WIPF1 regulates stemness in small cell lung cancer

ObjectiveSmall cell lung cancer (SCLC) is a highly malignant subtype of lung cancer. Cancer stem cell (CSC)-like cells have been implicated in chemoresistance and recurrence. Although previous studies have demonstrated the significance of WASP-interacting protein (WIPF1) in malignant tumors, its underlying molecular mechanism in SCLC is not well known. Here, we demonstrate that WIPF1 can regulate tumorigenesis and its underlying molecular mechanism in SCLC.MethodsSphere-formation culture effectively enriches CSC-like cells, such as tumor stem cell-like cells. RNA-seq was used to identify differentially expressed genes between enriched CSCs (3D cultures) and differentiated cells. Next, we adopted RNA interference techniques to investigate the effects of WIPF1 on colony and sphere-formation capacity, as well as cisplatin sensitivity in SCLC cells. Furthermore, we performed western blot analysis to analyze protein expression and employed the STRING database to identify potential signaling pathways.ResultsWIPF1 was significantly upregulated in sphere-formed SCLC cells, relative to differentiated ones under adherent growth conditions (2D cultures). The gene was involved in the regulation of colony formation, sphere-formation capacity, and cisplatin sensitivity in SCLC cell line model. Knocking down of WIPF1 significantly suppressed the proliferation of cancer cells via the YAP/TAZ protein.ConclusionsSphere-formation and chemoresistance represent indispensable characteristics of CSC-like cells. Notably, sphere-formation culture is a more effective approach for enriching of CSCs-like cells than traditional adherent culture. Upregulation of WIPF1 in sphere-formed cells, relative to differentiated ones, indicated that it plays an important role in the tumorigenesis of SCLC. Moreover, this process is mediated by the YAP/TAZ pathway, suggesting that it may be a potential therapeutic target for SCLC.