Src-mediated regulation of E-cadherin and EMT in pancreatic cancer.
The Src family of non receptor tyrosine kinases are integrators of divergent signal transduction pathways which regulate numerous cellular processes, including tumorigenicity and angiogenesis. In pancreatic adenocarcinoma, c-Src (Src) is frequently activated and results in increased tumor progression, invasion and metastasis. Dysfunction of the E-cadherin-mediated cell adhesion system plays an important role in tumor progression to invasive, metastatic carcinoma. Src has been shown to play a role in E-cadherin regulation and epithelial to mesenchymal transition (EMT). Increased Src activity promotes EMT while Src inhibition suppresses this process. Recent studies have focused on Src dependent regulation of E-cadherin and other tumor progression-related events such as EMT with the development of metastasis. Src has also been shown to be involved in chemoresistance of PDAC cells by promoting EMT. Although the molecular events associated with Src-dependent regulation of E-cadherin are becoming better defined, the cellular processes that trigger the onset of EMT remain unclear. Here we highlight recent work that advances our understanding of Src signaling as it relates to E-cadherin associated regulation and EMT in PDAC.
Division of Surgical Oncology, Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN 37232-6860, USA. nagaraj.nagathihalli@vanderbilt.edu
Nagaraj S
NS
Nagathihalli
Nipun B
NB
Merchant
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D015820:Cadherins; D047428:Protein Kinase Inhibitors; D014157:Transcription Factors; D019061:src-Family Kinases