TRIM32 promotes radioresistance by disrupting TC45-STAT3 interaction in triple-negative breast cancer

• Published in: Oncogene Vol. 41; no. 11; pp. 1589 - 1599
• Main Authors: Ma, Yan, Zhang, Haibo, Chen, Cheng, Liu, Lixin, Ding, Ting, Wang, Ying, Ma, Dachang, Ling, Xiaoling, Chen, Xiaohua, Li, Jianping, Guansheng, Zhong, Ru, Guoqing, Zhang, Lei, Tang, Jianming
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.03.2022; Nature Publishing Group
• Subjects: 13/1; 13/95; 38/77; 631/67/1059/485; 631/67/1347; 64/60; Apoptosis; Breast cancer; Cell Biology; Cell Line, Tumor; Cell Proliferation; Dephosphorylation; Gene Expression Regulation, Neoplastic; Human Genetics; Humans; Internal Medicine; Medical prognosis; Medicine; Medicine & Public Health; Molecular modelling; Oncology; Patients; Phosphorylation; Radiation therapy; Radioresistance; Stat3 protein; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Transcription activation; Transcription Factors - metabolism; Transcriptional Activation; Tripartite Motif Proteins - metabolism; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - radiotherapy; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/s41388-022-02204-1

Radioresistance is common in the treatment of triple-negative breast cancer (TNBC), but the molecular mechanisms involved remain unclear. Herein, we reveal that tripartite motif-containing protein 32 (TRIM32) is upregulated in TNBC and is negatively associated with survival of TNBC patients. Radiotherapy resulted in enhanced expression of TRIM32, whereas TRIM32 depletion reduced TNBC radioresistance in vitro and in vivo. Mechanistically, radiotherapy promoted the association between TRIM32 and nuclear STAT3, which suppressed TC45-induced dephosphorylation of STAT3, resulting in increased STAT3 transcriptional activation and TNBC radioresistance. Finally, we demonstrated that TRIM32 and STAT3 phosphorylation are co-expressed in TNBC tissues. Moreover, high expression of TRIM32 and STAT3 phosphorylation is positively linked to poor prognosis of TNBC patients. Our study demonstrates that TRIM32 is a novel target for predicting radioresistance in TNBC patients.