American Association for Cancer Research
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Figure S5 from Glucocorticoid Receptor Signaling Activates TEAD4 to Promote Breast Cancer Progression

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journal contribution
posted on 2023-03-31, 02:27 authored by Lingli He, Liang Yuan, Yang Sun, Pingyang Wang, Hailin Zhang, Xue Feng, Zuoyun Wang, Wenxiang Zhang, Chuanyu Yang, Yi Arial Zeng, Yun Zhao, Ceshi Chen, Lei Zhang

Supplementary Figure 5. TEAD4 shows no expression in Her2+ and ER+ breast cancer samples.

Funding

National Key Research and Development Program of China

National Natural Science Foundation of China

“Strategic Priority Research Program” of Chinese Academy of Sciences

Shanghai Leading Talents Program

Science and Technology Commission of Shanghai Municipality

Youth Innovation Promotion Association of the Chinese Academy of Sciences

History

ARTICLE ABSTRACT

The Hippo pathway plays a critical role in cell growth and tumorigenesis. The activity of TEA domain transcription factor 4 (TEAD4) determines the output of Hippo signaling; however, the regulation and function of TEAD4 has not been explored extensively. Here, we identified glucocorticoids (GC) as novel activators of TEAD4. GC treatment facilitated glucocorticoid receptor (GR)-dependent nuclear accumulation and transcriptional activation of TEAD4. TEAD4 positively correlated with GR expression in human breast cancer, and high expression of TEAD4 predicted poor survival of patients with breast cancer. Mechanistically, GC activation promoted GR interaction with TEAD4, forming a complex that was recruited to the TEAD4 promoter to boost its own expression. Functionally, the activation of TEAD4 by GC promoted breast cancer stem cells maintenance, cell survival, metastasis, and chemoresistance both in vitro and in vivo. Pharmacologic inhibition of TEAD4 inhibited GC-induced breast cancer chemoresistance. In conclusion, our study reveals a novel regulation and functional role of TEAD4 in breast cancer and proposes a potential new strategy for breast cancer therapy. This study provides new insight into the role of glucocorticoid signaling in breast cancer, with potential for clinical translation.