New insights into the regulation mechanism and function of TEAD4 in breast cancer
Source:
Time: 2020-03-17
Hippo pathway plays a critical role in cell growth and tumorigenesis. Since the activity of downstream effector TEAD4 determines the output of Hippo pathway, it is quite important to study the underlying regulation mechanism and function of TEAD4 that has not been explored extensively.
In a study published online in Cancer Research, research teams led by Prof. ZHANG Lei at Shanghai Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences and Prof. CHEN Ceshi at the Kunming Institute of Zoology, CAS, identified glucocorticoids (GCs) as novel activators of TEAD4. GCs treatment facilitates glucocorticoid receptor (GR)-dependent nuclear accumulation and transcriptional activation of TEAD4, which promotes TEAD4 transcriptional activity in turn.
Mechanistically, GCs-stimulated GR binds with TEAD4 and is recruited to the promoter of TEAD4 to drive TEAD4 transcriptional activation. Clinically, the expression of TEAD4 has positive correlation with GR in human breast cancer. GCs-induced TEAD4 activity is responsible for breast cancer cell survival, metastasis and chemo-resistance both
in vitro and
in vivo. Pharmacological inhibition of TEAD4 activity improves GCs-induced breast cancer chemo-resistance. This study reveals a novel regulation mechanism and function of TEAD4 in breast cancer and propose a potential
therapeutic target for breast cancer.
HE Lingli and her colleagues completed this work. The work was financially supported by the National Natural Science Foundation of China, National Natural Science, Shanghai Program, “Strategic Priority Research Program” of the
Chinese Academy of Sciences, the Youth Innovation Promotion Association Chinese Academy of Sciences and Chinese Academy of Sciences.
Working model
Contact: rayzhang@sibcb.ac.cn
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