Src, chemoresistance and epithelial to mesenchymal transition: are they related?
The Src family of nonreceptor tyrosine kinases regulates numerous cellular processes, including proliferation, differentiation, migration, survival and angiogenesis. In solid tumors, Src is frequently aberrantly active, and promotes tumor progression and metastasis. Although multiple Src functions may contribute to metastasis, recently Src has been shown to play a role in epithelial to mesenchymal transition. Increased Src activity promotes this process and inhibition of Src suppresses epithelial to mesenchymal transition. Although the molecular events causing epithelial to mesenchymal transition are becoming well defined, the processes in tumor cells that trigger the onset of this phenotype remain unclear. Recent studies have associated epithelial to mesenchymal transition with the development of chemoresistance. Src has also been shown to be involved in chemoresistance of cancer cells. The activation of Src in chemoresistant cells is related to an increase in motility, invasiveness and detachment, all phenotypes characteristic both of Src activation and of epithelial to mesenchymal transition. This review focuses on upregulation of Src in cancer as it relates to chemoresistance and epithelial to mesenchymal transition.
Shah
Ami N
AN
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Gallick
Gary E
GE
D000818:Animals; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009362:Neoplasm Metastasis / Q000503:physiopathology; D019061:src-Family Kinases / Q000502:physiology*
D019061:src-Family Kinases