Open AccessThe stabilization of yes‐associated protein by TGFβ‐activated kinase 1 regulates the self‐renewal and oncogenesis of gastric cancer stem cells
Author(s) -
Wang Gang,
Sun Qikai,
Zhu Hai,
Bi Yihui,
Zhu Haixing,
Xu Aman
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16660
Subject(s) - carcinogenesis , cancer research , sox2 , cancer stem cell , cancer , metastasis , stem cell , cancer cell , biology , immunohistochemistry , transcription factor , medicine , pathology , immunology , microbiology and biotechnology , biochemistry , gene
Abstract Gastric cancer (GC) is the most frequent digestive system malignant tumour and the second most common cause of cancer death globally. Cancer stem cell (CSC) is a small percentage of cancer cells in solid tumours that have differentiation, self‐renewal and tumorigenic capabilities. They have an active participation in the initiation, development, metastasis, recurrence and resistance of tumours to chemotherapy and radiotherapy. Gastric cancer stem cells (GCSCs) have been shown to be correlated with GC initiation and metastasis. In this study, we found that TAK1 expression level in GC tissues was significantly increased compared to the adjacent non‐cancerous tissues by RT‐qPCR, Western blot and immunohistochemistry. TAK1 has been identified as a critical molecule that promoted a variety of malignant GC phenotypes both in vivo and in vitro and promoted the self‐renewal of GCSCs. Mechanistically, TAK1 was up‐regulated by IL‐6 and prevented the degradation of yes‐associated protein (YAP) in the cytoplasm by binding to YAP. Thus, TAK1 promoted the SOX2 and SOX9 transcription and the self‐renewal and oncogenesis of GCSCs. Our findings provide insights into the mechanism of self‐renewal and tumorigenesis of TAK1 in GCSCs and have broad implications for clinical therapies.