Abstract
ACK1 is a nonreceptor tyrosine kinase with a unique structure, which is tightly related to the biological behavior of tumors. Previous studies have demonstrated that ACK1 was involved with multiple signaling pathways of tumor progression. Its crucial role in tumor cell proliferation, apoptosis, invasion, and metastasis was tightly related to the prognosis and clinicopathology of cancer. ACK1 has a unique way of regulating cellular pathways, different from other nonreceptor tyrosine kinases. As an oncogenic kinase, recent studies have shown that ACK1 plays a critical regulatory role in the initiation and progression of tumors. In this review, we will be summarizing the structural characteristics, activation, and regulation of ACK1 in breast cancer, aiming to deeply understand the functional and mechanistic role of ACK1 and provide novel therapeutic strategies for breast cancer treatment.
Highlights
Breast cancer is the most common type of cancer and the leading cause of cancer-related death among women worldwide [1]
The SAM domain was involved with the membrane localization, dimerization, and activation of ACK1 [18, 19]. e CRIB domain mediates the interaction between ACK1 and Cdc42 [3, 20], and the PPXY motif mediates the interaction between ACK1 and WW domain [21]. e MHR domain mediates the interaction between ACK1 and receptor tyrosine kinase [22]. e UBA domains are involved with the regulation of ACK1 binding to ubiquitin and its polyubiquitination and degradation [23]
Homeobox A1 (HOXA1) gene is a potent oncogene, and the active expression of HOXA1 is enough to cause the oncogenic transformation of human breast epithelial cells and has the ability of invasive tumor [50]. e expression of HOXA1 was significantly increased in regulatory therapy but was significantly downregulated in MCF-7 breast cancer cells treated with ACK1 inhibitor AIM-100 and dasatinib
Summary
Breast cancer is the most common type of cancer and the leading cause of cancer-related death among women worldwide [1]. Breast cancer research found that many ACK1 tyrosine kinase signaling proteins in many tumor cells are activated repeatedly [3,4,5,6]. ACK1 expression is positively correlated with the severity of the disease progression and negatively correlated with the survival rate in breast cancer patients [7, 8]. E process is tightly and dynamically controlled by a series of the single signal paths or multiple phosphorylation cascades and forms tyrosine kinase connection [3, 12]. It has been found that the overexpression of ACK1 is related to various tumors, including lung, prostate, stomach, pancreatic, breast, and ovarian cancers [8, 12,13,14,15,16]. Is review summarizes the function and mechanism of ACK1 in breast cancer, aiming to deeply understand the relationship between ACK1 and breast cancer and providing a basis for personalized treatment of breast cancer
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