Role of Notch1 Signaling Pathway in Small Cell Lung Carcinoma

Lung cancer is the leading cause of cancer-related death around the globe. It is generally divided into small-cell and non-small-cell lung carcinomas. Small-cell lung cancer (SCLC) is a malignant tumor characterized by rapid growth, high metastatic potential, and a frequent rate of relapse after chemotherapy. All the features may worse aggressiveness of this cancer and increase the possibility of unsuccessful therapeutic attempts. Notch1 signaling is a crucial molecular pathway in the regulation of many cellular functions, including cell-cell communication and gene regulation. Moreover, it was proposed previously that Notch1 might be oncogenic in various types of cancer, but the question arises as to why many SCLC cell lines do not express this pathway. This review aims to explore the role of this complex pathway in SCLC in both vitro and vivo studies and whether it has a tumor-promoting or suppressive effect. After an extensive literature review, it was found that the expression of Notch1 signaling in SCLC reduces its proliferative ability while promoting increased cell apoptosis. Furthermore, it reduces cell motility, invasion, and metastatic ability and enhances cell-cell adhesion by inhibiting epithelial-mesenchymal transition (EMT). Furthermore, it contributes to cell chemo-resistance by altering multidrug resistance-associated protein-1 (MRP-1), demonstrating an overall tumor-suppressive effect. Given these findings, induction of Notch1 using histone deacetylase inhibitor (HDACi) may be a potential future therapeutic strategy for SCLC management. Nevertheless, the effect of such a sophisticated signaling pathway in tumor carcinogenesis can't be generalized to all human cancers, and further studies are needed to better tailor therapeutic plans based on the specific cellular context.