title: The role of Src in colon cancer and its therapeutic implications.
abstract: Src is a member of a superfamily of membrane-associated nonreceptor protein tyrosine kinases. It is stimulated by receptors of growth hormone, cytokines, and adipokines, and it regulates multiple signaling pathways, including phosphatidylinositide 3 kinase-Akt, mitogen-activated protein kinase, signal transducer and activator of transcription 3, interleukin 8, and vascular endothelial growth factor pathways, and cytoskeletal pathways to cause a cascade of cellular responses. Eighty percent of patients with colon cancer overexpress Src in tumor tissue. Evidence has shown that the overexpression of Src in colon cancer accelerates metastasis and causes chemotherapeutic drug resistance via multiple downstream signaling pathways. Therefore, the inhibition of Src may be useful for the treatment of colon cancer. However, the inhibition of Src may also weaken immune responses that are essential for the eradication of cancer cells. Overcoming the problem of inhibiting Src in cancer cells while retaining immune system efficacy is the key to the successful application of Src-inhibition therapy. Different Src family members are used by the immune system and colon cancer. This differential use may provide a good opportunity to develop Src family member-specific inhibitors to avoid immune inhibition.
authors.affiliation: School of Biomedical Sciences, University of Queensland, St Lucia, Australia.
authors.forename: Jiezhong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Dana Farber Cancer Center, Boston, MA.
authors.forename: Aymen
authors.initials: A
authors.lastname: Elfiky
authors.affiliation: Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, Australia.
authors.forename: Mei
authors.initials: M
authors.lastname: Han
authors.affiliation: School of Biomedical Sciences, University of Queensland, St Lucia, Australia.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Gastrointestinal Colorectal Oncology Program and Experimental Therapeutics Program, Tufts Medical Center, Tufts University School of Medicine, Boston, MA. Electronic address: wsaif@tuftsmedicalcenter.org.
authors.forename: M Wasif
authors.initials: MW
authors.lastname: Saif
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D019061:src-Family Kinases / Q000502:physiology*
chemical_list: D019061:src-Family Kinases
keywords: Immune response; MAPK; Metastasis; PI3K/Akt; STAT3; Targeted therapy