Research Progress of the Functional Role of ACK1 in Breast Cancer

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.

Long and short non-coding RNA and radiation response: a review

“…57 ACK1 has been shown to be a tumor initiator and involved with tumor progression. 58 Similarly, Wu et al…”

Role of Activated Cdc42-Associated Kinase 1 (ACK1/TNK2)-Inhibitors in Precision Oncology

“…Role of Activated Cdc42-Associated Kinase 1 (ACK1/TNK2)-Inhibitors in Precision Oncology DOI: http://dx.doi.org/10.5772/intechopen.102343 severity progression and negatively correlated to the survival rate in breast cancer patients. [4,12,[26][27][28][29][30] However clinical trials of targeting ACK1 in triple negative breast cancers (TNBCs) have not shown any promising results with specific inhibitors. Many tyrosine kinases (EGFR), oncoproteins (AKT), tumor suppressor proteins (Wwox), and epigenetic modification regulatory proteins (KDM3A) interacts with ACK1 in breast cancer [4,[28][29][30][31][32].…”

“…As the inhibitors are developed by only limited methods (screening small molecules and fragment libraries), it have weak affinities which makes the selection of drug candidates difficult and time consuming. Further the development of allosteric inhibitors of ACK1 is also difficult as 1), ( 2), ( 3), ( 4), KRCA-0008 ( 5), (R)-9b ( 6), XMD8-87 (7), XMD16-5 (8), benzopyrimidodiaze-pinone derivatives (( 9), ( 10)). Adapted from Aoxue Wang et al [6].…”

“…Optimized structures of 14 multikinase inhibitors. The name for few multikinase inhibitors are GNF-1(1), Dasatinib (5), bosutinib (6), ceritinib (7), PD158780 (8), vemurafenib (9), ADZ9291 (10), sunitinib (11), flavopiridol (12), and gefitinib (13). Adapted from Srivastava [41].…”

“…ACK1 consists of 8 domains; sterile α motif domain (SAM), tyrosine kinase domain (TKD), Src homology 3 domain (SH3), Cdc42/Rac-interactive binding motif (CRIB), clathrinbinding region (CLATH), PPXY motif or WW domain-interacting region, epidermal growth factor receptor-binding domain (EBD) or Mig-6-homology region (MHR), and ubiquitin association domain (UBA). The SAM domain is related to membrane localization, dimerization, and activation of ACK1 (Figure 2) [7].…”