Role of c-Src in Carcinogenesis and Drug Resistance

Abstract

The aberrant transformation of normal cells into cancer cells, known as carcinogenesis, is a complex process involving numerous genetic and molecular alterations in response to innate and environmental stimuli. The Src family kinases (SFK) are key components of signaling pathways implicated in carcinogenesis, with c-Src and its oncogenic counterpart v-Src often playing a significant role. The discovery of c-Src represents a compelling narrative highlighting groundbreaking discoveries and valuable insights into the molecular mechanisms underlying carcinogenesis. Upon oncogenic activation, c-Src activates multiple downstream signaling pathways, including the PI3K-AKT pathway, the Ras-MAPK pathway, the JAK-STAT3 pathway, and the FAK/Paxillin pathway, which are important for cell proliferation, survival, migration, invasion, metastasis, and drug resistance. In this review, we delve into the discovery of c-Src and v-Src, the structure of c-Src, and the molecular mechanisms that activate c-Src. We also focus on the various signaling pathways that c-Src employs to promote oncogenesis and resistance to chemotherapy drugs as well as molecularly targeted agents.

UPLC-ESI-MS/MS-based widely targeted metabolomics reveals differences in metabolite composition among four Ganoderma species

“…In each PPI network, SRC, GAPDH, TNF, and AKT1 were among the top five highest-degree targets. SRC is associated with increased tumor progression, invasion, and metastasis in many cancers ( 74 , 75 ). TNF plays a crucial role in cancer treatment and autoimmunity ( 76 , 77 ), while AKT1 is linked to breast cancer and ovarian cancer ( 78 , 79 ).…”

Role of Protein Tyrosine Phosphatase Receptor Type E (PTPRE) in Chemoresistant Retinoblastoma

“…It has been reported that at the molecular level, PTPRE dephosphorylates and thereby activates SRC [9,19,20]. Activation of SRC has been shown to activate downstream pathways like, e.g., the PI3K-AKT pathway, playing an essential role in cell proliferation, survival, growth, tumor initiation, metastasis, and drug resistance (for review see: [26]). The activity of SRC is significantly reduced in tumor cells lacking PTPRE and restoring SRC activity revealed that it is only its reduced activity that caused aberrant proliferation rates of tumor cells lacking PTPRE [9].…”

“…PTPRE regulates phosphorylation processes with the involvement of different other kinases like SRC [10,20], ERK1/2 [23], glucocorticoid kinase 3 (SGK3) and AKT downstream signaling [24,25]. As all of the above-mentioned signaling molecules mediate effects related to cell proliferation, growth, viability, tumor initiation and tumor cell migration [26][27][28], effects likewise seen to be influenced following PTPRE silencing, we investigated ERK/p-ERK, SRC/pSRC, AKT/p-AKT, and SGK3/pSGK3 expression after PTPRE knockdown in order to reveal possible PTPRE downstream signaling mechanisms in etoposide-resistant RB cells.…”

Emerging Roles of YES1 in Cancer: The Putative Target in Drug Resistance

“…Consequently, numerous researchers are focused on identifying novel molecular biomarkers that could predict treatment responses and prevent tumor relapse. It has been reported that Src family kinases (SFKs) play a role in advancing oncogenesis and in conferring resistance to chemotherapy drugs as well as to molecular targeted therapies [2].…”