Non-Muscle Myosin IIC as a Prognostic and Therapeutic Target in Cancer

Cancer metastasis is associated with epithelial-mesenchymal transition (EMT), and NMII is linked to EMT. Calcium sensitization through ROCK activates myosin II, contributing to metastasis. NMII undergoes phosphorylation at Thr18/Ser19, affecting its function and involvement in processes like exocytosis, apoptosis, and transcellular intravasations. Inhibition of myosin II ATPase activity blocks cytokinesis, highlighting its role in cell cycle regulation. NMII has distinct binding motifs and sites for regulation, including Thr18/Ser19 via kinases/phosphatases, Ser1/Ser2/Thr9 via phosphokinase C, and involvement in cytokinesis via contractile ring formation. These characteristics make NMII a potential therapeutic target. NMII-C is found to be less expressive in glioma (40% low expression, 60% high expression), not showing prognostic value. However, in stomach cancer (35–65% expression) and renal cancer (40–60% expression), NMII-C appears to have prognostic significance. NMII-C’s prognostic value has not been reported in various other cancers, including thyroid, lung, liver, colorectal, urothelial, endometrial, head and neck, melanoma, prostate, testicular, pancreatic, breast, cervical, and ovarian cancers, highlighting a need for further research in these areas. Some pharmacological agents such as Blebbistatin, DT-13, Statins, and Y27632 have shown promising potential against NMII-C in cancer therapy, with positive results in pre-clinical studies and ongoing clinical trials. Understanding the specific functions and regulation of NMII isoforms, particularly NMII-C, may provide valuable insights into the development of targeted cancer therapies. Additionally, the study suggests that NMII-C may have prognostic importance in specific cancer stages, offering a foundation for further exploration of NMII-C’s mechanisms of action for future medical interventions.