The Regulators of Metastasis related Signalling Targets in Cancer Cells

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Medical Biology".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 12876

Special Issue Editors


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Guest Editor
Institute of Biotechnology, Gebze Technical University, Gebze 41400, Turkey
Interests: cell signalling; apoptosis; mTOR; AMPK
Special Issues, Collections and Topics in MDPI journals
St George's, University of London, London, UK
Interests: metastasis; bone; microRNA; androgens

Special Issue Information

Dear Colleagues,

Cell signalling pathways, which regulate cell growth, proliferation and survival mechanisms in cancer cells, are also crucial for the poor progression of disease.  Abnormal activation of these targets drives tumorigenesis with unlimited alterations in the tumour microenvironment and leads to metastasis through changing fundamental characteristics of cancer cells. A number of critical players have been identified, with their multiple roles in cell survival and metastasis-related cancer progression. Thus, the clarification of the responsible pathways and related biomarkers is currently under way using specific inhibitors and/or receptor blockers and promises to help identify potential therapeutic targets to develop successful cancer treatments. These research efforts are crucial to achieve new targeted therapy options with less adverse effects, which increase the life quality of patients.

The aim of this Special Issue is to evaluate the current therapeutic targets as well as to identify new key regulators of cell signalling pathways that are involved in cell survival and metastatic cascades.

Dr. Pinar Uysal Onganer
Dr. Elif Damla Arisan
Dr. Alwyn Dart
Guest Editors

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Keywords

  • cancer 
  • signalling 
  • pathway 
  • receptor 
  • crosstalk 
  • growth 
  • apoptosis metastasis

Published Papers (4 papers)

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Research

17 pages, 8910 KiB  
Article
The Expression of Signaling Genes in Breast Cancer Cells
by Jolanta Rzymowska, Andrzej Wilkołaski, Lidia Szatkowska and Ludmiła Grzybowska
Biology 2022, 11(4), 555; https://doi.org/10.3390/biology11040555 - 3 Apr 2022
Cited by 2 | Viewed by 2181
Abstract
The aim of the study was to investigate the effect of paclitaxel on the expression of genes encoding signaling factors in breast cancer cells in in vitro conditions after incubation with the said chemotherapeutic. The tested cells were harvested from the mammary glands [...] Read more.
The aim of the study was to investigate the effect of paclitaxel on the expression of genes encoding signaling factors in breast cancer cells in in vitro conditions after incubation with the said chemotherapeutic. The tested cells were harvested from the mammary glands of 36 patients with early breast cancer. The microarray technology was employed for the identification of gene expression. For this purpose, mRNA isolated from tumor cells was used. A significant effect of paclitaxel on the genome of breast cancer cells was confirmed. Paclitaxel changed the functions of cancer cells by increasing the expression of most genes encoding signaling proteins and receptors. The analysis of the results suggested that this cytostatic agent produces a beneficial therapeutic effect at a lower dose (60 ng/mL). In contrast, a high dose of paclitaxel (300 ng/mL) was associated with a high cytotoxicity. Full article
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20 pages, 2632 KiB  
Article
Prostate Cancer Cell Extracellular Vesicles Increase Mineralisation of Bone Osteoblast Precursor Cells in an In Vitro Model
by Ben Lanning, Jason Webber, Pinar Uysal-Onganer, Wen Guo Jiang, Aled Clayton and Dafydd Alwyn Dart
Biology 2021, 10(4), 318; https://doi.org/10.3390/biology10040318 - 10 Apr 2021
Cited by 7 | Viewed by 3454
Abstract
Skeletal metastases are the most common form of secondary tumour associated with prostate cancer (PCa). The aberrant function of bone cells neighbouring these tumours leads to the devel-opment of osteoblastic lesions. Communication between PCa cells and bone cells in bone envi-ronments governs both [...] Read more.
Skeletal metastases are the most common form of secondary tumour associated with prostate cancer (PCa). The aberrant function of bone cells neighbouring these tumours leads to the devel-opment of osteoblastic lesions. Communication between PCa cells and bone cells in bone envi-ronments governs both the formation/development of the associated lesion, and growth of the secondary tumour. Using osteoblasts as a model system, we observed that PCa cells and their conditioned medium could stimulate and increase mineralisation and osteoblasts’ differentiation. Secreted factors within PCa-conditioned medium responsible for osteoblastic changes included small extracellular vesicles (sEVs), which were sufficient to drive osteoblastogenesis. Using MiR-seq, we profiled the miRNA content of PCa sEVs, showing that miR-16-5p was highly ex-pressed. MiR-16 was subsequently higher in EV-treated 7F2 cells and a miR-16 mimic could also stimulate mineralisation. Next, using RNA-seq of extracellular vesicle (EV)-treated 7F2 cells, we observed a large degree of gene downregulation and an increased mineralisation. Ingenuity® Pathway Analysis (IPA®) revealed that miR-16-5p (and other miRs) was a likely upstream effec-tor. MiR-16-5p targets in 7F2 cells, possibly involved in osteoblastogenesis, were included for val-idation, namely AXIN2, PLSCR4, ADRB2 and DLL1. We then confirmed the targeting and dow-regulation of these genes by sEV miR-16-5p using luciferase UTR (untranslated region) reporters. Conversely, the overexpression of PLSCR4, ADRB2 and DLL1 lead to decreased osteoblastogene-sis. These results indicate that miR-16 is an inducer of osteoblastogenesis and is transmitted through prostate cancer-derived sEVs. The mechanism is a likely contributor towards the for-mation of osteoblastic lesions in metastatic PCa. Full article
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18 pages, 2537 KiB  
Article
Specific c-Jun N-Terminal Kinase Inhibitor, JNK-IN-8 Suppresses Mesenchymal Profile of PTX-Resistant MCF-7 Cells through Modulating PI3K/Akt, MAPK and Wnt Signaling Pathways
by Pelin Ozfiliz Kilbas, Ozlem Sonmez, Pinar Uysal-Onganer, Ajda Coker Gurkan, Pinar Obakan Yerlikaya and Elif Damla Arisan
Biology 2020, 9(10), 320; https://doi.org/10.3390/biology9100320 - 1 Oct 2020
Cited by 7 | Viewed by 3408
Abstract
Paclitaxel (PTX) is a widely used chemotherapeutic agent in the treatment of breast cancer, and resistance to PTX is a common failure of breast cancer therapy. Therefore, understanding the effective molecular targets in PTX-resistance gains importance in identifying novel strategies in successful breast [...] Read more.
Paclitaxel (PTX) is a widely used chemotherapeutic agent in the treatment of breast cancer, and resistance to PTX is a common failure of breast cancer therapy. Therefore, understanding the effective molecular targets in PTX-resistance gains importance in identifying novel strategies in successful breast cancer therapy approaches. The aim of the study was to investigate the functional role of PTX resistance on MCF-7 cell survival and proliferation related to PI3K/Akt and MAPK pathways. The generated PTX-resistant (PTX-res) MCF-7 cells showed enhanced cell survival, proliferation, and colony formation potential with decreased cell death compared to wt MCF-7 cells. PTX-res MCF-7 cells exhibited increased motility profile with EMT, PI3K/Akt, and MAPK pathway induction. According to the significant SAPK/JNK activation in PTX-res MCF-7 cells, specific c-Jun N-terminal kinase inhibitor, JNK-IN-8 is shown to suppress the migration potential of cells. Treatment of JNK inhibitor suppressed the p38 and SAPK/JNK and Vimentin expression. However, the JNK inhibitor further downregulated Wnt signaling members in PTX-res MCF-7 cells. Therefore, the JNK inhibitor JNK-IN-8 might be used as a potential therapy model to reverse PTX-resistance related to Wnt signaling. Full article
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18 pages, 4444 KiB  
Article
Inhibition on JNK Mimics Silencing of Wnt-11 Mediated Cellular Response in Androgen-Independent Prostate Cancer Cells
by Elif Damla Arisan, Ozge Rencuzogullari, Buse Keskin, Guy H. Grant and Pinar Uysal-Onganer
Biology 2020, 9(7), 142; https://doi.org/10.3390/biology9070142 - 27 Jun 2020
Cited by 2 | Viewed by 2706
Abstract
Prostate cancer (PCa) is one of the most common cancers among men, and one of the leading causes of cancer death for men. The c-Jun N-terminal kinase (JNK) pathway is required for several cellular functions, such as survival, proliferation, differentiation, and migration. Wnt-11, [...] Read more.
Prostate cancer (PCa) is one of the most common cancers among men, and one of the leading causes of cancer death for men. The c-Jun N-terminal kinase (JNK) pathway is required for several cellular functions, such as survival, proliferation, differentiation, and migration. Wnt-11, a member of the Wnt family, has been identified for its upregulation in PCa; however, downstream signalling of Wnt-11 remains to be fully characterized. In this study, we investigated the role of the JNK pathway as a potential downstream factor for Wnt-11 signalling. For this purpose, LNCaP, DU145, and PC-3 PCa cells and normal epithelial PNT1A cells were treated with a specific JNK kinase inhibitor: JNKVIII. Our results showed that JNK inhibition decreased mitochondrial membrane potential and promoted cell death in a cell type-dependent manner. We found that JNK inhibition led to an increase in autophagy and prevented epithelial–mesenchymal transition (EMT) in independently growing androgen cells. JNK inhibition and the silencing of Wnt-11 showed similar responses in DU145 and PC-3 cells and decreased metastasis-related biomarkers, cell migration, and invasion. Overall, our results suggest that JNK signalling plays a significant role in the pathophysiology of PCa by mediating Wnt-11 induced signals. Our data highlights that both the JNK pathway and Wnt-11 could be a useful therapeutic target for the combinatory application of current PCa. Full article
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