DOC‐2/DAB2 interactive protein destabilizes c‐Myc to impair the growth and self‐renewal of colon tumor‐repopulating cells

作者：Hai-Ou Li, Yunjiao Zhou, Meng Wang, Haizhou Wang, Yangyang Zhang, Ruyi Peng, Ruike Zhang, Meng Zhang, Mengna Zhang, Peishan Qiu, Lan Liu, Qiu Zhao, Jing Liu · 发表于：Cancer Science · 年份：2021 · DOI：10.1111/cas.15120 · 被引用次数：10 · 研究领域：Cancer Cells and Metastasis、Microtubule and mitosis dynamics、Wnt/β-catenin signaling in development and cancer

Colorectal carcinoma (CRC) remains a huge challenge in clinical treatment due to tumor metastasis and recurrence. Stem cell-like colon tumor-repopulating cells (TRCs) are a subpopulation of cancer cells with highly tumorigenic and chemotherapy resistant properties. The core transcription factor c-Myc is essential for maintaining cancer stem-like cell phenotypes, yet its roles and regulatory mechanisms remain unclear in colon TRCs. We report that elevated c-Myc protein supported formation and growth of TRC spheroids. The tumor suppressor DOC-2/DAB2 interactive protein (DAB2IP) suppressed c-Myc expression to inhibit TRC expansion and self-renewal. Particularly, DAB2IP disrupted c-Myc stability through glycogen synthase kinase 3β/protein phosphatase 2A-B56α-mediated phosphorylation and dephosphorylation cascade on c-Myc protein, leading to its eventual degradation through the ubiquitin-proteasome pathway. The expression of DAB2IP was negatively correlated with c-Myc in CRC specimens. Overall, our results improved mechanistic insight into how DAB2IP suppressed TRC growth and self-renewal.