The extracellular SEMA domain attenuates intracellular apoptotic signaling of semaphorin 6A in lung cancer cells. (December 2018) - Shen, Cheng-Ying
Abstract Semaphorin 6 A (SEMA6A ), a membrane-bound protein, is downregulated in lung cancer tissue compared to its adjacent normal tissue. However, the functions ofSEMA6A in lung cancer cells are still unclear. In the present study, full lengthSEMA6A and various truncations were transfected into lung cancer cells to investigate the role of the different domains ofSEMA6A in cell proliferation and survival, apoptosis, and in vivo tumor growth.SEMA6A -induced cell signaling was explored using gene silencing, co-immunoprecipitation, and co-culture assays. Our results showed that overexpression ofSEMA6A reduced the growth of lung cancer cells in vitro and in vivo, and silencingSEMA6A increased the proliferation of normal lung fibroblasts. Truncated SEMA6A lacking the SEMA domain or the extracellular region induced more apoptosis than full length SEMA6A, and reintroducing the SEMA domain attenuated the apoptosis. Fas-associated protein with death domain (FADD) bound to the cytosolic region of truncated SEMA6A and was involved in SEMA6A-associated cytosol-induced apoptosis. This study suggests a novel function ofSEMA6A in inducing apoptosis via FADD binding in lung cancer cells.