ER-α36: a novel biomarker and potential therapeutic target in breast cancer

Abstract

Xingyun Su,1 Xin Xu,1 Guangliang Li,1,4 Bingyi Lin,2 Jiang Cao,3 Lisong Teng1 1Department of Surgical Oncology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, People’s Republic of China; 3Clinical Research Center, The 2nd Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, People’s Republic of China Abstract: Estrogen receptor-alpha36 (ER-α36) is a 36-kDa variant of estrogen receptor-alpha (ER-α) firstly identified and cloned by Wang et al in 2005. It lacks both transactivation domains (activation function 1 and activation function 2) and has different biological characteristics compared to traditional ER-α (ER-α66). ER-α36 primarily locates on plasma membrane and cytoplasm and functions as a mediator in the rapid membrane-initiated non-genomic signaling pathway. Additionally, it inhibits the traditional genomic signaling pathway mediated by ER-α66 in a dominant-negative pattern. Accumulating evidence has demonstrated that ER-α36 regulates the physiological function of various tissues. Thus, dysregulation of ER-α36 is closely associated with plenty of diseases including cancers. ER-α36 is recognized as a molecular abnormality which solidly correlates to carcinogenesis, aggressiveness, and therapeutic response of breast cancer. Additionally, special attention has been paid to the role of ER-α36 in endocrine therapy resistance. Therefore, ER-α36 provides a novel biomarker of great value for diagnosis, prognosis, and treatment of breast cancer. It may also be a potential therapeutic target for breast cancer patients, especially for those who are resistant to endocrine therapy. In this review, we will overview and update the biological characteristics, underlying mechanism, and function of ER-α36, focusing on its biological function in breast cancer and endocrine therapy resistance. We will evaluate its application value in clinical practice. Keywords: ER, ER-α36, breast cancer, endocrine therapy resistance