MAP4K4 and WT1 mediate SOX6‐induced cellular senescence by synergistically activating the ATF2–TGFβ2–Smad2/3 signaling pathway in cervical cancer

• DOI: 10.1002/1878-0261.13613
• Publication Date: 2024-02-22T02:25:35Z
• Authors: Han Zheng; Mingchen Liu; Shu Shi; Hongxin Huang; Xingwen Yang; Ziheng Luo; Yarong Song; Qiang Xu; Tingting Li; Lixiang Xue; Fengmin Lu; Jie Wang
• Keywords: Senescence; Cellular senescence

SRY‐box transcription factor 6 ( SOX6 ) is a member of the SOX gene family and inhibits proliferation cervical cancer cells by inducing cell cycle arrest. However, final fate significance these cell‐cycle‐arrested induced remains unclear. Here, we report that cellular senescence, which mainly mediated promoting transforming growth beta 2 TGFB2 expression subsequently activating TGFβ2–Smad2/3–p53–p21 WAF1/CIP1 –Rb pathway. promotes through MAP4K4–MAPK (JNK/ERK/p38)–ATF2 WT1–ATF2 pathways, dependent on its high‐mobility group (HMG) domain. In addition, SOX6‐induced senescent are resistant to cisplatin treatment. ABT‐263 (navitoclax) ABT‐199 (venetoclax), two classic senolytics, can specifically eliminate cells, thus significantly improve chemosensitivity cisplatin‐resistant cells. This study uncovers MAP4K4/WT1–ATF2–TGFβ2 axis mediates promising therapeutic target in improving cancer.