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Role of motor proteins in human cancers
Iman Hassan Ibrahim1, Amany Balah2, Abrar Gomaa Abd Elfattah Hassan1
1Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Girls), Al-Azhar University, Postal code 11765, Egypt.
Abstract:
Motor proteins include several protein families (Kinesin, Dynein and Myosin) responsible for intracellular transport, intercellular communication, among other functions. In cancer cells, motor proteins along with microtubules (MT) and other tubulin and actin structures, are crucial for cell proliferation and invasion. The cBioPortal platform for Cancer Genomics database was queried for solid cancers in a combined cohort of 9204 patients with complete cancer genomics data. To assess the importance of motor proteins in cancer, copy number alterations (CNAs) and survival rates were analyzed in the combined dataset. Kinesin, Dynein, and Myosin families showed CNAs in 47%, 49%, and 57 % of patients, respectively, in at least one of their members. Survival analysis showed that CNAs in Kinesin and Dynein, families' genes in the same patients were significantly correlated to decreased overall survival. These results added more evidence to previous literature highlighting the importance of motor proteins as a target in cancer therapy. Kinesin inhibitors could act by several mechanisms such as inhibiting spindle assembly or centrosome separation during mitosis, leading to cell cycle arrest and eventually apoptosis. Dynein inhibitors modulate Dynein's activity and MT binding, inhibiting cell proliferation and invasion. Myosin inhibitors act by stabilizing MT, inducing cell cycle arrest and inhibiting invasiveness. Increasing the specificity of motor proteins targeting drugs could improve cancer therapy and patient survival.
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