Myosin Light Chains in the Progression of Cancer

Figures

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  Figure 1. Myosin Light Chain and the Tumor Cell Cycle. Myosin light chains act in the cell cycle, controlling proliferation. (A) MYL5 localizes to the spindle poles in early mitosis (G1/S) and remains until mitotic exit (G2/M) through its association with Myosin X (MYO10) [16]. (B) MYL6B is a tumor promoter which degrades p53 to cause aberrant control of cell cycle transitions leading to hyper proliferation and DNA damage [20]. (C) The contractile ring is regulated by Myl9 and Myl12a/Myl12b; however, Myl9 expression also extends or shortens G0/G1, controlling tumor re-initiation as well as proper cell division. This force is generated by NMII17. Figure made in Biorender.

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  Figure 2. Myosin light Chain and Metastasis. Myosin light chains have been implicated in various steps of the metastasis cascade. (A) Most often, depending upon the tumor origin type, tumors will acquire a more invasive phenotype by upregulation of invasive characteristics to enter the stroma and surrounding circulatory system. MYL9 expression is linked to the EMT process and responsible for the signaling pathways involved in such phenotypic changes [22,23] (B) A tumor microenvironment (TME) is a sophisticated niche supplying the tumor with vasculature, a process known as angiogenesis. MYL9 is critical for angiogenesis by activating actomyosin contractility and angiogenic sprouting. Highly contractile cells, such as cancer-associated fibroblasts, in the TME can remodel the ECM and promote metastasis. MYL9 supports the CAF phenotype [24,25,26]. (C) 1. Invasive cancer cells acquire various mechanisms for translocation and penetration through the stromal matrix and myosin light chains MYL5, MLC-2, MLC20, and MYL9 help cancer cells gain invasive properties through mechanotransduction and control of genetic factors [21,24,25,27,28,29,30]. 2. For metastasis to occur, a cancer cell must break…

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  Figure 3. Myosin Light chain in various cancer(s). Myosin light chains are implicated in causing cancer in different organs and tissues. From left to right, MYL1 promotes tumor metastasis in head and neck squamous cell carcinoma (HNSCC) and is an unfavorable prognostic marker [33]. Reduction in MYL9 is linked to better overall survival (OS), post progression survival (PPS), and relapse free survival (RFS) in breast cancer patients [34]. Low expression of MYL5 worsens the pathological stage and prognosis in breast cancer patients [34]. MYL6B is a tumor driver gene in hepatocellar carcinoma (HCC) and promotes the degradation of p53 tumor suppressor by MDM2 mediated ubiquitination [20]. MYL9 promotes liver metastases in vivo in late-stage colorectal cancer (CRC) [14]. The pattern of MYL9 expression in pancreatic cancer (PDAC) tissues correlates with poor prognosis in OS and distant metastases free survival [18]. MYL2 is involved in the pathogenesis of rhabdomyosarcoma and can aid in reducing mortality rates [42]. MYL3 expression levels are correlated with poor OS in patients with Ewing sarcoma [43]. High MYL9 expression is correlated with poor prognosis in newly diagnosed Glioblastoma…