SRC kinase-mediated signaling pathways and targeted therapies in breast cancer

Abstract

Breast cancer (BC) has been ranked the most common malignant tumor throughout the world and is also a leading cause of cancer-related deaths among women. SRC family kinases (SFKs) belong to the non-receptor tyrosine kinase (nRTK) family, which has eleven members sharing similar structure and function. Among them, SRC is the first identified proto-oncogene in mammalian cells. Oncogenic overexpression or activation of SRC has been revealed to play essential roles in multiple events of BC progression, including tumor initiation, growth, metastasis, drug resistance and stemness regulations. In this review, we will first give an overview of SRC kinase and SRC-relevant functions in various subtypes of BC and then systematically summarize SRC-mediated signaling transductions, with particular emphasis on SRC-mediated substrate phosphorylation in BC. Furthermore, we will discuss the progress of SRC-based targeted therapies in BC and the potential future direction.

Chitosan-loaded piperlongumine nanoparticles and kaempferol enhance the anti-cancer action of doxorubicin in targeting of Ehrlich solid adenocarcinoma: in vivo and in silico modeling study

“…Both PL and Kmp docked the active sites of the NF-kappaB-inducing kinase (NIK) and the Proto-Oncogene Tyrosine-Protein Kinase (SRC-kinase) successfully with a high negative energy value compared to their corresponding co-ligand inhibitors (Table 1 ). Considering their significant cancer-promoting role, targeting NIK [ 41 ], and SRC-kinase [ 42 ] has been recently shown as an effective anti-cancer-targeted therapy.…”

Prevention of radiotherapy-induced pro-tumorigenic microenvironment by SFK-inhibitors

“…This study emphasizes SFKs as a main regulator in the development of a radiotherapy-induced protumorigenic microenvironment. SFKs, a family of non-receptor protein tyrosine kinases, is recognized for its involvement in various cellular processes, including proliferation, differentiation, and apoptosis 13,14 .…”

“…SRC family kinases (SFKs), a family of non-receptor protein tyrosine kinases, play a crucial role in signal transduction of various cellular processes in cancer cells 13,14 . The roles and mechanisms of SFKs in tumorigenesis have been extensively investigated, and SFKs recently have been recognized as potential targets for anti-cancer therapy [14][15][16] . Nevertheless, research on the functions of SFKs and their targeting in other cell types within the tumor microenvironment is limited.…”

Targeting Breast Cancer: The Familiar, the Emerging, and the Uncharted Territories

“…While the Src family of kinases has been long identified and investigated as a protein involved in breast cancer and hyperactivated in many types of cancer, it has just recently become an attractive target for molecularly targeted drugs due to gaps in knowledge in its role and activation mechanisms [ 47 ]. The role of these non-receptor kinases has been indicated in a variety of mechanisms involved in the progression of breast cancer (including metastasis and resistance) [ 121 ]. Src is activated by a wide array of membrane receptors (including EGFR and HER2); however, it is also reported to provide positive feedback for activation of these receptors ( Figure 4 ), which means that Src activation does not necessarily require HER2 signaling [ 39 ].…”