STK38 is a critical upstream regulator of MYC's oncogenic activity in human B-cell lymphoma

• Published in: Oncogene Vol. 32; no. 45; pp. 5283 - 5291
• Main Authors: Bisikirska, B C, Adam, S J, Alvarez, M J, Rajbhandari, P, Cox, R, Lefebvre, C, Wang, K, Rieckhof, G E, Felsher, D W, Califano, A
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 07.11.2013
• Subjects: Animals; Apoptosis; B-Lymphocytes - metabolism; Carcinogenesis; Cell Line, Tumor; Cell Transformation, Neoplastic - genetics; Cells; Gene Expression Regulation, Neoplastic; Genes; Genetic aspects; HEK293 Cells; HeLa Cells; Heterografts; Humans; Lymphoma; Lymphoma, B-Cell - metabolism; Mice; Mice, SCID; Neoplasm Transplantation; Phosphotransferases; Properties; Protein Processing, Post-Translational; Protein-protein interactions; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proteins; Proto-Oncogene Proteins c-myc - metabolism; Receptors, Antigen, B-Cell - metabolism; RNA Interference; RNA, Small Interfering; Testing; Tumors
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2012.543

The MYC protooncogene is associated with the pathogenesis of most human neoplasia. Conversely, its experimental inactivation elicits oncogene addiction. Besides constituting a formidable therapeutic target, MYC also has an essential function in normal physiology, thus creating the need for context-specific targeting strategies. The analysis of post-translational MYC activity modulation yields novel targets for MYC inactivation. Specifically, following regulatory network analysis in human B-cells, we identify a novel role of the STK38 kinase as a regulator of MYC activity and a candidate target for abrogating tumorigenesis in MYC-addicted lymphoma. We found that STK38 regulates MYC protein stability and turnover in a kinase activity-dependent manner. STK38 kinase inactivation abrogates apoptosis following B-cell receptor activation, whereas its silencing significantly decreases MYC levels and increases apoptosis. Moreover, STK38 knockdown suppresses growth of MYC-addicted tumors in vivo, thus providing a novel viable target for treating these malignancies.