TMEM120B strengthens breast cancer cell stemness and accelerates chemotherapy resistance via β1-integrin/FAK-TAZ-mTOR signaling axis by binding to MYH9

作者：Ran Hu, Yu Cao, Yuanyuan Wang, Tingting Zhao, Kaibo Yang, Mingwei Fan, Mengyao Guan, Yuekang Hou, Jiao Ying, Xiaowen Ma, Ning Deng, Xun Sun, Yong Zhang, Xiupeng Zhang · 发表于：Breast Cancer Research · 年份：2024 · DOI：10.1186/s13058-024-01802-z · 被引用次数：24 · 研究领域：Hippo pathway signaling and YAP/TAZ、Cancer Cells and Metastasis、Cell Adhesion Molecules Research

BACKGROUND: Breast cancer stem cell (CSC) expansion results in tumor progression and chemoresistance; however, the modulation of CSC pluripotency remains unexplored. Transmembrane protein 120B (TMEM120B) is a newly discovered protein expressed in human tissues, especially in malignant tissues; however, its role in CSC expansion has not been studied. This study aimed to determine the role of TMEM120B in transcriptional coactivator with PDZ-binding motif (TAZ)-mediated CSC expansion and chemotherapy resistance. METHODS: Both bioinformatics analysis and immunohistochemistry assays were performed to examine expression patterns of TMEM120B in lung, breast, gastric, colon, and ovarian cancers. Clinicopathological factors and overall survival were also evaluated. Next, colony formation assay, MTT assay, EdU assay, transwell assay, wound healing assay, flow cytometric analysis, sphere formation assay, western blotting analysis, mouse xenograft model analysis, RNA-sequencing assay, immunofluorescence assay, and reverse transcriptase-polymerase chain reaction were performed to investigate the effect of TMEM120B interaction on proliferation, invasion, stemness, chemotherapy sensitivity, and integrin/FAK/TAZ/mTOR activation. Further, liquid chromatography-tandem mass spectrometry analysis, GST pull-down assay, and immunoprecipitation assays were performed to evaluate the interactions between TMEM120B, myosin heavy chain 9 (MYH9), and CUL9. RESULTS: TMEM120B expression was elevated in lun...