SnoN/SkiL, a TGFβ signaling mediator: a participant in autophagy induced by arsenic trioxide.
Effective treatment of cancer cells with chemotherapeutic drugs relies on their ability to induce cell death, making the discovery of their mechanisms of action crucial. Arsenic trioxide (As(2)O(3)), used in the treatment of promyelocytic leukemia (PML), triggers cell death in several solid tumor cell lines including ovarian carcinomas. While As(2)O(3) is remarkably cytotoxic in human ovarian cancer cells, its mechanism of action is poorly understood. We recently investigated the effects of As(2)O(3) on several transforming growth factor-β (TGFβ) signaling mediators to better understand its cell death mechanism. Indeed, dysregulated (TGFβ) signaling is typical of ovarian cancers. Based on our findings, we propose that As(2)O(3) induces a Beclin 1-independent autophagic pathway in ovarian carcinoma cells by modulating SnoN/SkiL expression, implicating SnoN as a novel therapeutic target for ovarian cancers.
Raffoul
Fadi
F
Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL, USA.
Campla
Christie
C
Nanjundan
Meera
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D010087:Oxides / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000970:Antineoplastic Agents; D001152:Arsenicals; D047908:Intracellular Signaling Peptides and Proteins; D010087:Oxides; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; C060615:SKIL protein, human; D016212:Transforming Growth Factor beta; D000077237:Arsenic Trioxide