KCNF1 is a Novel Regulator of NSCLC Cell Growth Independent of Its Potassium Ion Channel Function
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Lung cancer is the leading cause of cancer-related deaths worldwide. Non-Small Cell Lung Cancer (NSCLC) is the most common type of lung cancer and is associated with a poor 5-year overall survival rate. In recent years, ion channels have emerged as a putative oncogenic target in cancer research. The aberrant expression of ion channels contributes to several hallmarks of cancer that include uncontrolled growth, evading cell death, cell migration/invasion, and induction of angiogenesis in several types of human cancers. Thus, making ion channels as novel molecular targets in the field of cancer. This thesis aims to identify the unique role of an electrically silent voltage-gated potassium ion channel (KCNF1, a.k.a Kv5.1) in NSCLC progression. Interestingly, silencing KCNF1 in NSCLC cell lines via small interference RNA (siRNA)-mediated knock down showed: 1) decreased cell proliferation and 2) reduced cell migration/invasion. Furthermore, through in vitro and in vivo assays, KCNF1 was found to be inversely correlated and a downstream target of Wnt7A- a member of Wnt Signaling Pathway and a tumor suppressor in lung cancer. To elucidate whether its effects in NSCLC cell growth operates via K+ ion channel function, whole cell patch clamp recordings were performed. Interestingly, stable KCNF1 knockdown cells, as well as Wnt7a expressing cells, showed no significant changes in K+ ion channel currents. Thus, signifying that KCNF1 acts independent of K+ ion channel function. In summary, by using several molecular biology, cell biology, and electrophysiological assays, KCNF1 was identified as a tumor promoter in lung cancer, independent of K+ channel activity. Hence, KCNF1 represents a novel target for the development of future therapies in lung cancer.
SubjectNSCLC, KCNF1, Wnt7a, Potassium ion channel