REC8 enhances stemness and promotes metastasis of colorectal cancer through BTK/Akt/β-catenin signaling pathway

Translational Oncology

Ruolin Cui¹  Ting Liu¹  Shuling Wang¹  Jiuna Zhang¹  Xue Zhou¹  Huiqing Jiang¹  Xiaoli Xie¹  Ning Kang¹  Xiaoxu Jin¹  Yongjuan Wang¹  Dongxuan Zhang¹  Yijun Wang¹  Ran Qi²  Shengxiong Chen³  Shiying Dou⁴ 

[1] Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, China;Department of General Practice, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China;Department of Hepatobiliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China;Department of Infectious Diseases, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China;

关键词: Rec8 meiotic recombination protein;    Colorectal cancer;    Cancer stem cell;    Stemness;    Metastasis;   

DOI  :  

来源: DOAJ

【 摘 要 】

Cancer/testis antigens (CTAs) are often aberrantly expressed in cancer stem cells (CSCs) which are responsible for tumor metastasis. Rec8 meiotic recombination protein (REC8), a member of CTAs, shares distinct roles in various cancers, while its contribution to CSCs and colorectal cancer (CRC) remains unclear. We found that overexpression of REC8 facilitated the migration and invasion of CRC cells (DLD-1 and SW480 cells) in vitro and promoted the liver metastasis of CRC in vivo. Moreover, REC8 is highly expressed in CRC stem-like cells and is required for the maintenance of CSC stemness. Mechanistic studies suggested that REC8 mediated through the activation of Bruton tyrosine kinase (BTK). Inhibition of BTK by ibrutinib not only suppressed the migration and invasion-promoting ability, but also declined the increased expression of p-BTK, p-Akt, β-catenin, and CSC markers upon REC8 overexpression. Importantly, high expression of REC8 in cancerous tissues was related to advanced clinical stage and lymph node metastasis of 62 CRC patients, and REC8 was enriched in the cancerous cells positive for CSC markers. Collectively, our results indicate that REC8 promotes CRC metastasis by increasing cell stemness through BTK/Akt/β-catenin pathway.

【 授权许可】

Unknown