Kinases and Phosphatases

15 pages, 323 KiB

Open AccessReview

Cancer Stem Cell Metastatic Checkpoints and Glycosylation Patterns: Implications for Therapeutic Strategies

by Sara Sadat Aghamiri and Rada Amin

Kinases Phosphatases 2024, 2(2), 151-165; https://doi.org/10.3390/kinasesphosphatases2020009 - 22 Apr 2024

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Cancer stem cells (CSCs), found within tumors, are powerful drivers of disease recurrence and metastasis. Their abilities to self-renew and maintain stem-like properties make treatment difficult, as their heterogeneity and metastatic properties can lead to resistance and limit the effectiveness of standard therapies. Given their significance, CSCs are typically isolated based on combinations of markers, which often indicate heterogeneous populations of CSCs. The lack of consensus in cell characterization poses challenges in defining and targeting these cells for effective therapeutic interventions. In this review, we suggest five promising molecules—ABCB5, CD26, CD66c, uPAR, and Trop-2—chosen specifically for their distinct distribution within cancer types and clinical relevance. These markers, expressed at the cell surface of CSCs, could significantly enhance the specificity of cancer stemness characterization. This review focuses on describing their pivotal roles as biomarker checkpoints for metastasis. Additionally, this review outlines existing literature on glycosylation modifications, which present intriguing epitopes aimed at modulating the stability and function of these markers. Finally, we summarize several promising in vivo and clinical trial approaches targeting the mentioned surface markers, offering potential solutions to overcome the therapeutic resistance of CSCs and addressing current gaps in treatment strategies. Full article

15 pages, 2638 KiB

Open AccessArticle

Short-Chain Fatty Acids Suppress mTOR Signaling in Colon Cancer Cells via Long Non-Coding RNA RMST

by Jiuhui Wang, Yande Guo, Xiangwei Fang, Yuanqin Zhang and Daotai Nie

Kinases Phosphatases 2024, 2(2), 136-150; https://doi.org/10.3390/kinasesphosphatases2020008 - 01 Apr 2024

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Abstract

Short-chain fatty acids (SCFAs), derived from fermentation of dietary fibers and resistant starch by the microbiota in the colon, exert multiple effects on colonic functions, including tumor suppressing activities. Our previous studies found that SCFAs induced autophagy in colon cancer cells via downregulating mTOR signaling, but the mechanism involved in mTOR suppression still needs to be defined. In this study, we identified rhabdomyosarcoma 2 associated transcript (RMST), a long non-coding RNA, as a key mediator for SCFAs to suppress mTOR activation in colon cancer cells. RMST could be significantly induced by SCFAs in a time- and dose-dependent manner. RMST, by itself, was sufficient to suppress mTOR signaling and augment autophagosome formation. Depletion of RMST, through siRNA or CRISPR knockdown, reduced the abilities of SCFAs to suppress mTOR activation or to induce autophagic responses. RMST increased the expression level of TSC2, a negative regulator of the mTOR signaling pathway. Our data delineate a novel RMST/TSC2 cellular pathway, enlisted by SCFAs, to modulate mTOR activities in colon cancer cells. Full article

(This article belongs to the Special Issue The PI3K Pathway in Human Disease from the Bench to the Clinic: There and Back Again)

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26 pages, 8307 KiB

Open AccessReview

CK2 Inhibitors Targeting Inside and Outside the Catalytic Box

by Sophie Day-Riley, Rebekah M. West, Paul D. Brear, Marko Hyvönen and David R. Spring

Kinases Phosphatases 2024, 2(2), 110-135; https://doi.org/10.3390/kinasesphosphatases2020007 - 26 Mar 2024

Viewed by 1079

Abstract

CK2 is a protein kinase that plays an important role in numerous cellular pathways involved in cell growth, differentiation, proliferation, and death. Consequently, upregulation of CK2 is implicated in many disease types, in particular cancer. As such, CK2 has gained significant attention as a potential therapeutic target in cancer, and over 40 chemical probes targeting CK2 have been developed in the past decade. In this review, we highlighted several chemical probes that target sites outside the conventional ATP-binding site. These chemical probes belong to different classes of molecules, from small molecules to peptides, and possess different mechanisms of action. Many of the chemical probes discussed in this review could serve as promising new candidates for drugs selectively targeting CK2. Full article

(This article belongs to the Special Issue Past, Present and Future of Protein Kinase CK2 Research)

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Kinases Phosphatases, Volume 2, Issue 2 (June 2024) – 3 articles

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