Editorial

4 pages, 221 KiB

Open AccessEditorial

An Approach to Cell Motility as a Key Mechanism in Oncology

by José I. López and Ildefonso M. De la Fuente

Cancers 2021, 13(14), 3576; https://doi.org/10.3390/cancers13143576 - 16 Jul 2021

Viewed by 1500

Motility is an inherent characteristic of living cells manifesting cell migration, a fundamental mechanism of survival and development [...] Full article

(This article belongs to the Special Issue Cell Motility and Cancer)

Research

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16 pages, 24572 KiB

Open AccessArticle

LRG1 Promotes Metastatic Dissemination of Melanoma through Regulating EGFR/STAT3 Signalling

by Yuet Ping Kwan, Melissa Hui Yen Teo, Jonathan Chee Woei Lim, Michelle Siying Tan, Graciella Rosellinny, Walter Wahli and Xiaomeng Wang

Cancers 2021, 13(13), 3279; https://doi.org/10.3390/cancers13133279 - 30 Jun 2021

Cited by 14 | Viewed by 3496

Abstract

Although less common, melanoma is the deadliest form of skin cancer largely due to its highly metastatic nature. Currently, there are limited treatment options for metastatic melanoma and many of them could cause serious side effects. A better understanding of the molecular mechanisms [...] Read more.

Although less common, melanoma is the deadliest form of skin cancer largely due to its highly metastatic nature. Currently, there are limited treatment options for metastatic melanoma and many of them could cause serious side effects. A better understanding of the molecular mechanisms underlying the complex disease pathophysiology of metastatic melanoma may lead to the identification of novel therapeutic targets and facilitate the development of targeted therapeutics. In this study, we investigated the role of leucine-rich α-2-glycoprotein 1 (LRG1) in melanoma development and progression. We first established the association between LRG1 and melanoma in both human patient biopsies and mouse melanoma cell lines and revealed a significant induction of LRG1 expression in metastatic melanoma cells. We then showed no change in tumour cell growth, proliferation, and angiogenesis in the absence of the host Lrg1. On the other hand, there was reduced melanoma cell metastasis to the lungs in Lrg1-deficient mice. This observation was supported by the promoting effect of LRG1 in melanoma cell migration, invasion, and adhesion. Mechanistically, LRG1 mediates melanoma cell invasiveness in an EGFR/STAT3-dependent manner. Taken together, our studies provided compelling evidence that LRG1 is required for melanoma metastasis but not growth. Targeting LRG1 may offer an alternative strategy to control malignant melanoma. Full article

(This article belongs to the Special Issue Cell Motility and Cancer)

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25 pages, 10232 KiB

Open AccessArticle

The Plasma Membrane Ca²⁺ Pump PMCA4b Regulates Melanoma Cell Migration through Remodeling of the Actin Cytoskeleton

by Randa Naffa, Rita Padányi, Attila Ignácz, Zoltán Hegyi, Bálint Jezsó, Sarolta Tóth, Karolina Varga, László Homolya, Luca Hegedűs, Katalin Schlett and Agnes Enyedi

Cancers 2021, 13(6), 1354; https://doi.org/10.3390/cancers13061354 - 17 Mar 2021

Cited by 9 | Viewed by 2523

Abstract

We demonstrated that the plasma membrane Ca²⁺ ATPase PMCA4b inhibits migration and metastatic activity of BRAF mutant melanoma cells. Actin dynamics are essential for cells to move, invade and metastasize, therefore, we hypothesized that PMCA4b affected cell migration through remodeling of the [...] Read more.

We demonstrated that the plasma membrane Ca²⁺ ATPase PMCA4b inhibits migration and metastatic activity of BRAF mutant melanoma cells. Actin dynamics are essential for cells to move, invade and metastasize, therefore, we hypothesized that PMCA4b affected cell migration through remodeling of the actin cytoskeleton. We found that expression of PMCA4b in A375 BRAF mutant melanoma cells induced a profound change in cell shape, cell culture morphology, and displayed a polarized migratory character. Along with these changes the cells became more rounded with increased cell–cell connections, lamellipodia and stress fiber formation. Silencing PMCA4b in MCF-7 breast cancer cells had a similar effect, resulting in a dramatic loss of stress fibers. In addition, the PMCA4b expressing A375 cells maintained front-to-rear Ca²⁺ concentration gradient with the actin severing protein cofilin localizing to the lamellipodia, and preserved the integrity of the actin cytoskeleton from a destructive Ca²⁺ overload. We showed that both PMCA4b activity and trafficking were essential for the observed morphology and motility changes. In conclusion, our data suggest that PMCA4b plays a critical role in adopting front-to-rear polarity in a normally spindle-shaped cell type through F-actin rearrangement resulting in a less aggressive melanoma cell phenotype. Full article

(This article belongs to the Special Issue Cell Motility and Cancer)

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14 pages, 2202 KiB

Open AccessArticle

Targeting PVT1 Exon 9 Re-Expresses Claudin 4 Protein and Inhibits Migration by Claudin—Low Triple Negative Breast Cancer Cells

by Fayola Levine and Olorunseun O. Ogunwobi

Cancers 2021, 13(5), 1046; https://doi.org/10.3390/cancers13051046 - 02 Mar 2021

Cited by 8 | Viewed by 2290

Abstract

PVT1 is a long non-coding RNA transcribed from a gene located at the 8q24 chromosomal region that has been implicated in multiple cancers including breast cancer (BC). Amplification of the 8q24 chromosomal region is a common event in BC and is associated with [...] Read more.

PVT1 is a long non-coding RNA transcribed from a gene located at the 8q24 chromosomal region that has been implicated in multiple cancers including breast cancer (BC). Amplification of the 8q24 chromosomal region is a common event in BC and is associated with poor clinical outcomes. Claudin–low (CL) triple negative breast cancer (TNBC) is a subtype of BC with a particularly dismal outcome. We assessed PVT1 exon 9 expression in the T47D estrogen receptor positive BC cell line, and in the MDA MB 468 and MDA MB 231 TNBC cell lines, followed by the assessment of the expression of claudins 1, 3, 4 and 7, in MDA MB 468 and MDA MB 231 (TNBC) cells. We found that MDA MB 231 TNBC cells significantly express less claudin 1, 3, 4, and 7 than MDA MB 468 TNBC cells. PVT1 exon 9 is significantly upregulated in MDA MB 231 CL TNBC cells, and significantly downregulated in MDA MB 468 claudin high (CH) TNBC cells, in comparison to T47D estrogen receptor positive BC cells. We then analyzed the functional consequences of siRNA targeting of PVT1 exon 9 expression in the MDA MB 231 CL TNBC cells. Notably, siRNA targeting of PVT1 exon 9 expression in the MDA MB 231 CL TNBC cells led to a significant reduction in migration and the re-expression of claudin 4. Taken together, our data indicate that PVT1 exon 9 regulates claudin 4 expression and migration in CL TNBC cells, and may have clinical implications in CL TNBC. Full article

(This article belongs to the Special Issue Cell Motility and Cancer)

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19 pages, 3097 KiB

Open AccessArticle

Implications of ABCC4–Mediated cAMP Efflux for CRC Migration

by Jakub Kryczka, Ewelina Sochacka, Izabela Papiewska-Pająk and Joanna Boncela

Cancers 2020, 12(12), 3547; https://doi.org/10.3390/cancers12123547 - 27 Nov 2020

Cited by 12 | Viewed by 2182

Abstract

Colorectal cancer (CRC) presents significant molecular heterogeneity. The cellular plasticity of epithelial to mesenchymal transition (EMT) is one of the key factors responsible for the heterogeneous nature of metastatic CRC. EMT is an important regulator of ATP binding cassette (ABC) protein expression; these [...] Read more.

Colorectal cancer (CRC) presents significant molecular heterogeneity. The cellular plasticity of epithelial to mesenchymal transition (EMT) is one of the key factors responsible for the heterogeneous nature of metastatic CRC. EMT is an important regulator of ATP binding cassette (ABC) protein expression; these proteins are the active transporters of a broad range of endogenous compounds and anticancer drugs. In our previous studies, we performed a transcriptomic and functional analysis of CRC in the early stages of metastasis induced by the overexpression of Snail, the transcription factor involved in EMT initiation. Interestingly, we found a correlation between the Snail expression and ABCC4 (MRP4) protein upregulation. The relationship between epithelial transition and ABCC4 expression and function in CRC has not been previously defined. In the current study, we propose that the ABCC4 expression changes during EMT and may be differentially regulated in various subpopulations of CRC. We confirmed that ABCC4 upregulation is correlated with the phenotype conversion process in CRC. The analysis of Gene Expression Omnibus (GEO) sets showed that the ABCC4 expression was elevated in CRC patients. The results of a functional study demonstrated that, in CRC, ABCC4 can regulate cell migration in a cyclic nucleotide-dependent manner. Full article

(This article belongs to the Special Issue Cell Motility and Cancer)

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18 pages, 5472 KiB

Open AccessArticle

Mifepristone Treatment Promotes Testicular Leydig Cell Tumor Progression in Transgenic Mice

by Donata Ponikwicka-Tyszko, Marcin Chrusciel, Kamila Pulawska, Piotr Bernaczyk, Maria Sztachelska, Peilan Guo, Xiangdong Li, Jorma Toppari, Ilpo T. Huhtaniemi, Slawomir Wołczyński and Nafis A. Rahman

Cancers 2020, 12(11), 3263; https://doi.org/10.3390/cancers12113263 - 04 Nov 2020

Cited by 10 | Viewed by 3083

Abstract

The selective progesterone receptor modulator mifepristone (MF) may act as a potent antiproliferative agent in different steroid-dependent cancers due to its strong antagonistic effect on the nuclear progesterone receptor (PGR). Hereby, we analyzed the effects of MF treatment on Leydig cell tumor (LCT) [...] Read more.

The selective progesterone receptor modulator mifepristone (MF) may act as a potent antiproliferative agent in different steroid-dependent cancers due to its strong antagonistic effect on the nuclear progesterone receptor (PGR). Hereby, we analyzed the effects of MF treatment on Leydig cell tumor (LCT) progression in a transgenic mouse model (inhibin-α promoter-driven SV40 T-antigen), as well as on LCT (BLTK-1 and mLTC-1) cell proliferation. MF significantly stimulated the proliferation of LCT in vitro. Similarly, a 1-mo MF or P4 treatment stimulated LCT tumor growth in vivo. Traceable/absent classical Pgr or nonclassical membrane PRs α, β, γ and Pgrmc2, but abundant membrane Pgrmc1 expression, was found in LCTs. MF did not activate glucocorticoid or androgen receptors in LCTs. Functional analysis showed that PGRMC1 is required for MF and P4 to stimulate the proliferation and invasiveness of LCTs. Accordingly, MF and P4 induced PGRMC1 translocation into the nucleus and thereby stimulated the release of TGFβ1 in LCT cells. MF and P4 treatments upregulated Tgfbr1, Tgfbr2, and Alk1 expression and stimulated TGFβ1 release in LCT cells. Our findings provide novel mechanistic insights into the action of MF as a membrane PR agonist that promotes LCT growth through PGRMC1 and the alternative TGFβ1 signaling pathway. Full article

(This article belongs to the Special Issue Cell Motility and Cancer)

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25 pages, 4430 KiB

Open AccessArticle

SNAIL Promotes Metastatic Behavior of Rhabdomyosarcoma by Increasing EZRIN and AKT Expression and Regulating MicroRNA Networks

by Klaudia Skrzypek, Marta Kot, Paweł Konieczny, Artur Nieszporek, Anna Kusienicka, Małgorzata Lasota, Wojciech Bobela, Urszula Jankowska, Sylwia Kędracka-Krok and Marcin Majka

Cancers 2020, 12(7), 1870; https://doi.org/10.3390/cancers12071870 - 11 Jul 2020

Cited by 15 | Viewed by 3135

Abstract

Rhabdomyosarcoma (RMS) is a predominant soft tissue tumor in children and adolescents. For high-grade RMS with metastatic involvement, the 3-year overall survival rate is only 25 to 30%. Thus, understanding the regulatory mechanisms involved in promoting the metastasis of RMS is important. Here, [...] Read more.

Rhabdomyosarcoma (RMS) is a predominant soft tissue tumor in children and adolescents. For high-grade RMS with metastatic involvement, the 3-year overall survival rate is only 25 to 30%. Thus, understanding the regulatory mechanisms involved in promoting the metastasis of RMS is important. Here, we demonstrate for the first time that the SNAIL transcription factor regulates the metastatic behavior of RMS both in vitro and in vivo. SNAIL upregulates the protein expression of EZRIN and AKT, known to promote metastatic behavior, by direct interaction with their promoters. Our data suggest that SNAIL promotes RMS cell motility, invasion and chemotaxis towards the prometastatic factors: HGF and SDF-1 by regulating RHO, AKT and GSK3β activity. In addition, miRNA transcriptome analysis revealed that SNAIL-miRNA axis regulates processes associated with actin cytoskeleton reorganization. Our data show a novel role of SNAIL in regulating RMS cell metastasis that may also be important in other mesenchymal tumor types and clearly suggests SNAIL as a promising new target for future RMS therapies. Full article

(This article belongs to the Special Issue Cell Motility and Cancer)

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19 pages, 5006 KiB

Open AccessArticle

Tspan8 Drives Melanoma Dermal Invasion by Promoting ProMMP-9 Activation and Basement Membrane Proteolysis in a Keratinocyte-Dependent Manner

by Manale El Kharbili, Muriel Cario, Nicolas Béchetoille, Catherine Pain, Claude Boucheix, Françoise Degoul, Ingrid Masse and Odile Berthier-Vergnes

Cancers 2020, 12(5), 1297; https://doi.org/10.3390/cancers12051297 - 21 May 2020

Cited by 17 | Viewed by 3165

Abstract

Melanoma is the most aggressive skin cancer with an extremely challenging therapy. The dermal-epidermal junction (DEJ) degradation and subsequent dermal invasion are the earliest steps of melanoma dissemination, but the mechanisms remain elusive. We previously identified Tspan8 as a key actor in melanoma [...] Read more.

Melanoma is the most aggressive skin cancer with an extremely challenging therapy. The dermal-epidermal junction (DEJ) degradation and subsequent dermal invasion are the earliest steps of melanoma dissemination, but the mechanisms remain elusive. We previously identified Tspan8 as a key actor in melanoma invasiveness. Here, we investigated Tspan8 mechanisms of action during dermal invasion, using a validated skin-reconstruct-model that recapitulates melanoma dermal penetration through an authentic DEJ. We demonstrate that Tspan8 is sufficient to induce melanoma cells’ translocation to the dermis. Mechanistically, Tspan8⁺ melanoma cells cooperate with surrounding keratinocytes within the epidermis to promote keratinocyte-originated proMMP-9 activation process, collagen IV degradation and dermal colonization. This concurs with elevated active MMP-3 and low TIMP-1 levels, known to promote MMP-9 activity. Finally, a specific Tspan8-antibody reduces proMMP-9 activation and dermal invasion. Overall, our results provide new insights into the role of keratinocytes in melanoma dermal colonization through a cooperative mechanism never reported before, and establish for the first time the pro-invasive role of a tetraspanin family member in a cell non-autonomous manner. This work also displays solid arguments for the use of Tspan8-blocking antibodies to impede early melanoma spreading and therefore metastasis. Full article

(This article belongs to the Special Issue Cell Motility and Cancer)

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15 pages, 2440 KiB

Open AccessArticle

Adhesion and Migration Response to Radiation Therapy of Mammary Epithelial and Adenocarcinoma Cells Interacting with Different Stiffness Substrates

by Valeria Panzetta, Giuseppe La Verde, Mariagabriella Pugliese, Valeria Artiola, Cecilia Arrichiello, Paolo Muto, Marco La Commara, Paolo A. Netti and Sabato Fusco

Cancers 2020, 12(5), 1170; https://doi.org/10.3390/cancers12051170 - 06 May 2020

Cited by 17 | Viewed by 2945

Abstract

The structural and mechanical properties of the microenvironmental context have a profound impact on cancer cell motility, tumor invasion, and metastasis formation. In fact, cells react to their mechanical environment modulating their adhesion, cytoskeleton organization, changes of shape, and, consequently, the dynamics of [...] Read more.

The structural and mechanical properties of the microenvironmental context have a profound impact on cancer cell motility, tumor invasion, and metastasis formation. In fact, cells react to their mechanical environment modulating their adhesion, cytoskeleton organization, changes of shape, and, consequently, the dynamics of their motility. In order to elucidate the role of extracellular matrix stiffness as a driving force in cancer cell motility/invasion and the effects of ionizing radiations on these processes, we evaluated adhesion and migration as biophysical properties of two different mammary cell lines, over a range of pathophysiological stiffness (1–13 kPa) in a control condition and after the exposure to two different X-ray doses (2 and 10 Gy, photon beams). We concluded that the microenvironment mimicking the normal mechanics of healthy tissue has a radioprotective role on both cell lines, preventing cell motility and invasion. Supraphysiological extracellular matrix stiffness promoted tumor cell motility instead, but also had a normalizing effect on the response to radiation of tumor cells, lowering their migratory capability. This work lays the foundation for exploiting the extracellular matrix-mediated mechanism underlying the response of healthy and tumor cells to radiation treatments and opens new frontiers in the diagnostic and therapeutic use of radiotherapy. Full article

(This article belongs to the Special Issue Cell Motility and Cancer)

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Review

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24 pages, 1837 KiB

Open AccessReview

Syndecan-4 in Tumor Cell Motility

by Aniko Keller-Pinter, Szuzina Gyulai-Nagy, Daniel Becsky, Laszlo Dux and Laszlo Rovo

Cancers 2021, 13(13), 3322; https://doi.org/10.3390/cancers13133322 - 01 Jul 2021

Cited by 19 | Viewed by 4572

Abstract

Syndecan-4 (SDC4) is a ubiquitously expressed, transmembrane proteoglycan bearing heparan sulfate chains. SDC4 is involved in numerous inside-out and outside-in signaling processes, such as binding and sequestration of growth factors and extracellular matrix components, regulation of the activity of the small GTPase Rac1, [...] Read more.

Syndecan-4 (SDC4) is a ubiquitously expressed, transmembrane proteoglycan bearing heparan sulfate chains. SDC4 is involved in numerous inside-out and outside-in signaling processes, such as binding and sequestration of growth factors and extracellular matrix components, regulation of the activity of the small GTPase Rac1, protein kinase C-alpha, the level of intracellular calcium, or the phosphorylation of focal adhesion kinase. The ability of this proteoglycan to link the extracellular matrix and actin cytoskeleton enables SDC4 to contribute to biological functions like cell adhesion and migration, cell proliferation, cytokinesis, cellular polarity, or mechanotransduction. The multiple roles of SDC4 in tumor pathogenesis and progression has already been demonstrated; therefore, the expression and signaling of SDC4 was investigated in several tumor types. SDC4 influences tumor progression by regulating cell proliferation as well as cell migration by affecting cell-matrix adhesion and several signaling pathways. Here, we summarize the general role of SDC4 in cell migration and tumor cell motility. Full article

(This article belongs to the Special Issue Cell Motility and Cancer)

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14 pages, 966 KiB

Open AccessReview

Does Cancer Biology Rely on Parrondo’s Principles?

by Jean-Pascal Capp, Aurora M Nedelcu, Antoine M Dujon, Benjamin Roche, Francesco Catania, Beata Ujvari, Catherine Alix-Panabières and Frédéric Thomas

Cancers 2021, 13(9), 2197; https://doi.org/10.3390/cancers13092197 - 03 May 2021

Cited by 7 | Viewed by 2855

Abstract

Many aspects of cancer biology remain puzzling, including the proliferative and survival success of malignant cells in spite of their high genetic and epigenetic instability as well as their ability to express migrating phenotypes and/or enter dormancy despite possible fitness loss. Understanding the [...] Read more.

Many aspects of cancer biology remain puzzling, including the proliferative and survival success of malignant cells in spite of their high genetic and epigenetic instability as well as their ability to express migrating phenotypes and/or enter dormancy despite possible fitness loss. Understanding the potential adaptive value of these phenotypic traits is confounded by the fact that, when considered separately, they seem to be rather detrimental at the cell level, at least in the short term. Here, we argue that cancer’s biology and success could frequently be governed by processes underlying Parrondo’s paradox, whereby combinations of intrinsically losing strategies may result in winning outcomes. Oncogenic selection would favor Parrondo’s dynamics because, given the environmental adversity in which malignant cells emerge and evolve, alternating between various less optimal strategies would represent the sole viable option to counteract the changing and deleterious environments cells are exposed to during tumorigenesis. We suggest that malignant processes could be viewed through this lens, and we discuss how Parrondo’s principles are also important when designing therapies against cancer. Full article

(This article belongs to the Special Issue Cell Motility and Cancer)

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25 pages, 3003 KiB

Open AccessReview

PPARs and Tumor Microenvironment: The Emerging Roles of the Metabolic Master Regulators in Tumor Stromal–Epithelial Crosstalk and Carcinogenesis

by Hong Sheng Cheng, Yun Sheng Yip, Eldeen Kai Yi Lim, Walter Wahli and Nguan Soon Tan

Cancers 2021, 13(9), 2153; https://doi.org/10.3390/cancers13092153 - 29 Apr 2021

Cited by 34 | Viewed by 5423

Abstract

Peroxisome proliferator-activated receptors (PPARs) have been extensively studied for more than three decades. Consisting of three isotypes, PPARα, γ, and β/δ, these nuclear receptors are regarded as the master metabolic regulators which govern many aspects of the body energy homeostasis and cell fate. [...] Read more.

Peroxisome proliferator-activated receptors (PPARs) have been extensively studied for more than three decades. Consisting of three isotypes, PPARα, γ, and β/δ, these nuclear receptors are regarded as the master metabolic regulators which govern many aspects of the body energy homeostasis and cell fate. Their roles in malignancy are also increasingly recognized. With the growing interest in crosstalk between tumor stroma and epithelium, this review aims to highlight the current knowledge on the implications of PPARs in the tumor microenvironment. PPARγ plays a crucial role in the metabolic reprogramming of cancer-associated fibroblasts and adipocytes, coercing the two stromal cells to become substrate donors for cancer growth. Fibroblast PPARβ/δ can modify the risk of tumor initiation and cancer susceptibility. In endothelial cells, PPARβ/δ and PPARα are pro- and anti-angiogenic, respectively. Although the angiogenic role of PPARγ remains ambiguous, it is a crucial regulator in autocrine and paracrine signaling of cancer-associated fibroblasts and tumor-associated macrophages/immune cells. Of note, angiopoietin-like 4 (ANGPTL4), a secretory protein encoded by a target gene of PPARs, triggers critical oncogenic processes such as inflammatory signaling, extracellular matrix derangement, anoikis resistance and metastasis, making it a potential drug target for cancer treatment. To conclude, PPARs in the tumor microenvironment exhibit oncogenic activities which are highly controversial and dependent on many factors such as stromal cell types, cancer types, and oncogenesis stages. Thus, the success of PPAR-based anticancer treatment potentially relies on innovative strategies to modulate PPAR activity in a cell type-specific manner. Full article

(This article belongs to the Special Issue Cell Motility and Cancer)

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27 pages, 2970 KiB

Open AccessEditor’s ChoiceReview

Cytoskeletal Dynamics in Epithelial-Mesenchymal Transition: Insights into Therapeutic Targets for Cancer Metastasis

by Arpita Datta, Shuo Deng, Vennila Gopal, Kenneth Chun-Hong Yap, Clarissa Esmeralda Halim, Mun Leng Lye, Mei Shan Ong, Tuan Zea Tan, Gautam Sethi, Shing Chuan Hooi, Alan Prem Kumar and Celestial T. Yap

Cancers 2021, 13(8), 1882; https://doi.org/10.3390/cancers13081882 - 14 Apr 2021

Cited by 72 | Viewed by 7706

Abstract

In cancer cells, a vital cellular process during metastasis is the transformation of epithelial cells towards motile mesenchymal cells called the epithelial to mesenchymal transition (EMT). The cytoskeleton is an active network of three intracellular filaments: actin cytoskeleton, microtubules, and intermediate filaments. These [...] Read more.

In cancer cells, a vital cellular process during metastasis is the transformation of epithelial cells towards motile mesenchymal cells called the epithelial to mesenchymal transition (EMT). The cytoskeleton is an active network of three intracellular filaments: actin cytoskeleton, microtubules, and intermediate filaments. These filaments play a central role in the structural design and cell behavior and are necessary for EMT. During EMT, epithelial cells undergo a cellular transformation as manifested by cell elongation, migration, and invasion, coordinated by actin cytoskeleton reorganization. The actin cytoskeleton is an extremely dynamic structure, controlled by a balance of assembly and disassembly of actin filaments. Actin-binding proteins regulate the process of actin polymerization and depolymerization. Microtubule reorganization also plays an important role in cell migration and polarization. Intermediate filaments are rearranged, switching to a vimentin-rich network, and this protein is used as a marker for a mesenchymal cell. Hence, targeting EMT by regulating the activities of their key components may be a potential solution to metastasis. This review summarizes the research done on the physiological functions of the cytoskeleton, its role in the EMT process, and its effect on multidrug-resistant (MDR) cancer cells—highlight some future perspectives in cancer therapy by targeting cytoskeleton. Full article

(This article belongs to the Special Issue Cell Motility and Cancer)

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11 pages, 1272 KiB

Open AccessReview

The Multifaceted Roles of EGFL7 in Cancer and Drug Resistance

by Beate Heissig, Yousef Salama, Satoshi Takahashi, Ko Okumura and Koichi Hattori

Cancers 2021, 13(5), 1014; https://doi.org/10.3390/cancers13051014 - 01 Mar 2021

Cited by 13 | Viewed by 3492

Abstract

Invasion of cancer cells into surrounding tissue and the vasculature is an important step for tumor progression and the establishment of distant metastasis. The extracellular matrix (ECM) is home to many biomolecules that support new vessel formation and cancer growth. Endothelial cells release [...] Read more.

Invasion of cancer cells into surrounding tissue and the vasculature is an important step for tumor progression and the establishment of distant metastasis. The extracellular matrix (ECM) is home to many biomolecules that support new vessel formation and cancer growth. Endothelial cells release growth factors such as epidermal growth factor-like protein-7 (EGFL7), which contributes to the formation of the tumor vasculature. The signaling axis formed by EGFL7 and one of its receptors, beta 3 integrin, has emerged as a key mediator in the regulation of tumor metastasis and drug resistance. Here we summarize recent studies on the role of the ECM-linked angiocrine factor EGFL7 in primary tumor growth, neoangiogenesis, tumor metastasis by enhancing epithelial-mesenchymal transition, alterations in ECM rigidity, and drug resistance. We discuss its role in cellular adhesion and migration, vascular leakiness, and the anti-cancer response and provide background on its transcriptional regulation. Finally, we discuss its potential as a drug target as an anti-cancer strategy. Full article

(This article belongs to the Special Issue Cell Motility and Cancer)

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15 pages, 1098 KiB

Open AccessFeature PaperReview

Cell Motility and Cancer

by Ildefonso M. De la Fuente and José I. López

Cancers 2020, 12(8), 2177; https://doi.org/10.3390/cancers12082177 - 05 Aug 2020

Cited by 14 | Viewed by 3839

Abstract

Cell migration is an essential systemic behavior, tightly regulated, of all living cells endowed with directional motility that is involved in the major developmental stages of all complex organisms such as morphogenesis, embryogenesis, organogenesis, adult tissue remodeling, wound healing, immunological cell activities, angiogenesis, [...] Read more.

Cell migration is an essential systemic behavior, tightly regulated, of all living cells endowed with directional motility that is involved in the major developmental stages of all complex organisms such as morphogenesis, embryogenesis, organogenesis, adult tissue remodeling, wound healing, immunological cell activities, angiogenesis, tissue repair, cell differentiation, tissue regeneration as well as in a myriad of pathological conditions. However, how cells efficiently regulate their locomotion movements is still unclear. Since migration is also a crucial issue in cancer development, the goal of this narrative is to show the connection between basic findings in cell locomotion of unicellular eukaryotic organisms and the regulatory mechanisms of cell migration necessary for tumor invasion and metastases. More specifically, the review focuses on three main issues, (i) the regulation of the locomotion system in unicellular eukaryotic organisms and human cells, (ii) how the nucleus does not significantly affect the migratory trajectories of cells in two-dimension (2D) surfaces and (iii) the conditioned behavior detected in single cells as a primitive form of learning and adaptation to different contexts during cell migration. New findings in the control of cell motility both in unicellular organisms and mammalian cells open up a new framework in the understanding of the complex processes involved in systemic cellular locomotion and adaptation of a wide spectrum of diseases with high impact in the society such as cancer. Full article

(This article belongs to the Special Issue Cell Motility and Cancer)

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