MTA1 regulation of ER beta pathway in salivary gland carcinoma cells

作者：Ohshiro Kazufumi^*; Kumar Rakesh

来源：Biochemical and Biophysical Research Communications, 2015, 464(4): 1016-1021.

DOI：10.1016/j.bbrc.2015.07.043

• Coregulators
• Estrogen receptor beta
• Growth regulation
• Salivary gland cancer
• Cell migration

Although Metastatic-tumor antigen 1 (MTA1) is differentially expressed in metastatic cancer arid coregulates the status and activity of nuclear receptors, its role upon estrogen receptor beta (ER beta) - a potent tumor suppressor, remains poorly understood. Here we investigated whether MTA1 regulates the expression and functions of ER beta, an ER isoform predominantly expressed in salivary gland cancer cells. We found that the depletion of the endogenous MTA1 in the HSG and HSY salivary duct carcinoma cell lines enhances the expression of ER beta while MTA1 overexpression augmented the expression of ER beta in salivary duct carcinoma cells. Furthermore, MTA1 knockdown inhibited the proliferations and invasion of HSG and HSY cells. The noted ER beta downregulation by MTA1 overexpression involves the process of proteasomal degradation, as a proteasome inhibitor could block it. In addition, both MTA1 knockdown and ER beta overexpression attenuated the cell migration and inhibited the ERK1/2 signaling in the both cell lines. These findings imply that MTA1 dysregulation in a subset of salivary gland cancer might promote aggressive phenotypes by compromising the tumor suppressor activity of ER beta, and hence, MTA1-ER beta axis might serve a new therapeutic target for the salivary gland cancer.

• 出版日期2015-9-4