Cancer Discovery • Vol 12 • No 9
SMYD3 Impedes Small Cell Lung Cancer Sensitivity to Alkylation Damage through RNF113A Methylation–Phosphorylation Cross-talk
July 2022 • Valentina Lukinović, Simone Hausmann, Gaël Roth, Clément Oyeniran, Tanveer Ahmad, Ning Tsao, Joshua R. Brickner, Alexandre G. Casanova, Florent Chuff…
Abstract Small cell lung cancer (SCLC) is the most fatal form of lung cancer, with dismal survival, limited therapeutic options, and rapid development of chemoresistance. We identified the lysine methyltransferase SMYD3 as a major regulator of SCLC sensitivity to alkylation-based chemotherapy. RNF113A methylation by SMYD3 impairs its interaction with the phosphatase PP4, controlling its phosphorylation levels. This cross-talk between posttranslational modifications acts as a key switch in promoting and maintaining…