{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hu L"],"funding":["NIA NIH HHS","Medical Research Council","National Cancer Institute","NCI NIH HHS","National Institutes of Health","Cancer Prevention and Research Institute of Texas"],"pagination":["776-790.e5"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10922811"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["84(4)"],"pubmed_abstract":["TANK-binding kinase 1 (TBK1) is a potential therapeutic target in multiple cancers, including clear cell renal cell carcinoma (ccRCC). However, targeting TBK1 in clinical practice is challenging. One approach to overcome this challenge would be to identify an upstream TBK1 regulator that could be targeted therapeutically in cancer specifically. In this study, we perform a kinome-wide small interfering RNA (siRNA) screen and identify doublecortin-like kinase 2 (DCLK2) as a TBK1 regulator in ccRCC. DCLK2 binds to and directly phosphorylates TBK1 on Ser172. Depletion of DCLK2 inhibits anchorage-independent colony growth and kidney tumorigenesis in orthotopic xenograft models. Conversely, overexpression of DCLK2<sup>203</sup>, a short isoform that predominates in ccRCC, promotes ccRCC cell growth and tumorigenesis in vivo. Mechanistically, DCLK2<sup>203</sup> elicits its oncogenic signaling via TBK1 phosphorylation and activation. Taken together, these results suggest that DCLK2 is a TBK1 activator and potential therapeutic target for ccRCC."],"journal":["Molecular cell"],"pubmed_title":["Kinome-wide siRNA screen identifies a DCLK2-TBK1 oncogenic signaling axis in clear cell renal cell carcinoma."],"pmcid":["PMC10922811"],"funding_grant_id":["R01CA273595","R01 CA163834","R01 CA284591","R01CA211732","R01 CA211732","P50CA196516","R01CA163834","P30 CA142543","P50 CA196516","R01CA284591","MR/X01293X/1","R01 CA273595","R35CA197684","R35 CA197684","RR190058","R21 AG071229"],"pubmed_authors":["Liu H","Fang J","Zhang H","Liao C","Zhang Q","Guo L","Mendell JT","Li B","Chen X","Baldwin AS","Zhang C","Kapur P","Zhou J","Xu L","Xie L","von Kriegsheim A","Brugarolas J","Zhang Y","Luo M","Zhang X","Luo W","Zhong H","Zhu X","Hu L","Yao H"],"additional_accession":[]},"is_claimable":false,"name":"Kinome-wide siRNA screen identifies a DCLK2-TBK1 oncogenic signaling axis in clear cell renal cell carcinoma.","description":"TANK-binding kinase 1 (TBK1) is a potential therapeutic target in multiple cancers, including clear cell renal cell carcinoma (ccRCC). However, targeting TBK1 in clinical practice is challenging. One approach to overcome this challenge would be to identify an upstream TBK1 regulator that could be targeted therapeutically in cancer specifically. In this study, we perform a kinome-wide small interfering RNA (siRNA) screen and identify doublecortin-like kinase 2 (DCLK2) as a TBK1 regulator in ccRCC. DCLK2 binds to and directly phosphorylates TBK1 on Ser172. Depletion of DCLK2 inhibits anchorage-independent colony growth and kidney tumorigenesis in orthotopic xenograft models. Conversely, overexpression of DCLK2<sup>203</sup>, a short isoform that predominates in ccRCC, promotes ccRCC cell growth and tumorigenesis in vivo. Mechanistically, DCLK2<sup>203</sup> elicits its oncogenic signaling via TBK1 phosphorylation and activation. Taken together, these results suggest that DCLK2 is a TBK1 activator and potential therapeutic target for ccRCC.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-06-03T01:14:00.821Z","creation":"2025-04-19T13:42:34.701Z"},"accession":"S-EPMC10922811","cross_references":{"pubmed":["38211588"],"doi":["10.1016/j.molcel.2023.12.010"]}}