Pharmacological targeting of MYC-regulated IRE1/XBP1 pathway suppresses MYC-driven breast cancer

• Published in: The Journal of clinical investigation Vol. 128; no. 4; pp. 1283 - 1299
• Main Authors: Zhao, Na, Cao, Jin, Xu, Longyong, Tang, Qianzi, Dobrolecki, Lacey E., Lv, Xiangdong, Talukdar, Manisha, Lu, Yang, Wang, Xiaoran, Hu, Dorothy Z., Shi, Qing, Xiang, Yu, Wang, Yunfei, Liu, Xia, Bu, Wen, Jiang, Yi, Li, Mingzhou, Gong, Yingyun, Sun, Zheng, Ying, Haoqiang, Yuan, Bo, Lin, Xia, Feng, Xin-Hua, Hartig, Sean M., Li, Feng, Shen, Haifa, Chen, Yiwen, Han, Leng, Zeng, Qingping, Patterson, John B., Kaipparettu, Benny Abraham, Putluri, Nagireddy, Sicheri, Frank, Rosen, Jeffrey M., Lewis, Michael T., Chen, Xi
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.04.2018
• Subjects: Activating transcription factor 1; Animal models; Animals; Biomedical research; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer therapies; Cancer treatment; Care and treatment; Cell Line, Tumor; Chemotherapy; Development and progression; Docetaxel - pharmacology; Drug Delivery Systems; Endoplasmic reticulum; Endoribonucleases - genetics; Endoribonucleases - metabolism; Enzymes; Female; Genes; Genetic aspects; Genetic engineering; Health aspects; Humans; Inositol; Kinases; Mice; Molecular modelling; Myc protein; Nucleotidases; Pharmacological research; Phosphorylation; Physiological aspects; Protein folding; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proteins; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Response Elements; Ribonuclease; Saccharomyces cerevisiae; Signal Transduction - drug effects; Signal Transduction - genetics; Stem cells; Transcription; Transcription factors; Tumors; Unfolded Protein Response - drug effects; Unfolded Protein Response - genetics; X-Box Binding Protein 1 - genetics; X-Box Binding Protein 1 - metabolism; Xenograft Model Antitumor Assays; Xenografts; United States > US; Oncology; Breast cancer; Cell stress; Drug therapy; Therapeutics

The unfolded protein response (UPR) is a cellular homeostatic mechanism that is activated in many human cancers and plays pivotal roles in tumor progression and therapy resistance. However, the molecular mechanisms for UPR activation and regulation in cancer cells remain elusive. Here, we show that...