Scientists Reveal New Mechanism for Breast Cancer Tamoxifen Resistance

Jun 17, 2014     Email"> PrintText Size

Breast cancer is the second most common type of cancer and the leading cause of cancer death in women worldwide. Tamoxifen is the first-line drug in estrogen receptor-positive breast cancer therapy. However, patients suffer from acquired tamoxifen resistance and metastasis. The frequent distant metastasis after therapy implicates that resistance to anti-cancer drugs might be the intrinsic characteristic of metastatic cancer cells. Cancer cells utilize epithelial-mesenchymal transition (EMT) program to gain invasion and metastasis capability. It, however, remains unknown whether EMT directly contributes to the acquisition of tomaxifen resistant. 

 

In collaboration with Dr. ZHU Tao at Hefei National Laboratory for Physical Sciences, PhD students JIANG Yan and ZHAO Xiaotong, supervised by Dr. GE Gaoxiang at the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences discovered that EMT transcription factors Snail and Slug induce breast cancer tamoxifen resistance by activating EGFR-ERK signaling.

They further discovered that disruption of adherens junction alone is not sufficient to activate EGFR-ERK pathway and induce tamoxifen resistance. Low level Snail expression induces tamoxifen resistance, but is not able to induce EMT. EGFR-ERK pathway is not involved in the transition to, or maintenance of, mesenchymal phenotype. Thus, expression of Snail/Slug in breast cancer cells gives rise to EMT and tamoxifen resistance via distinct signaling pathways and effecter molecules (Figure). 

This work, entitled “Snail and Slug mediate tamoxifen resistance in breast cancer cells through activation of EGFR-ERK independent of epithelial-mesenchymal transition”, was published online in Journal of Molecular Cell Biology on June 11, 2014. It was supported by grants from the National Natural Science Foundation of China and the Ministry of Science and Technology of China. 

 

Expression of EMT transcription factors in breast cancer cells gives rise to EMT and tamoxifen resistance via independent signaling pathways and effecter molecules. (Image by Prof. GE Gaoxiang’s group)