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Elevated c-Src is linked to altered cell-matrix adhesion rather than proliferation in KM12C human colorectal cancer cells.

Jones RJ, Avizienyte E, Wyke AW, Owens DW, Brunton VG, Frame MC - Br. J. Cancer (2002)

Bottom Line: Elevated expression and/or activity of c-Src, the prototype of the Src family of protein tyrosine kinases, is associated with the development of human colon cancer.Although elevated Src correlates with ability to metastasise to the liver after intrasplenic injection, we found that this was not linked to enhanced growth, either in vitro or in vivo as sub-cutaneous tumours.However, elevated Src was associated with enhanced attachment to extracellular matrix.

View Article: PubMed Central - PubMed

Affiliation: Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, Scotland, UK.

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(A) Immunoblots showing expression (upper panel) and activity (lower panel) of c-Src in the poorly metastatic cell line, KM12C, and in their highly metastatic derivative cell lines, KM12SM and KM12L4A. Activity was assessed by reactivity with a phospho-specific antibody raised against the region of c-Src containing tyrosine-416, the presumed site of autophosphorylation. (B) Comparison of paxillin tyrosine phosphorylation in KM12C and KM12L4A cells. Paxillin was immunoprecipitated, blotted and probed with phosphotyrosine-specific antibodies (upper panel) or anti-paxillin (lower panel).
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fig1: (A) Immunoblots showing expression (upper panel) and activity (lower panel) of c-Src in the poorly metastatic cell line, KM12C, and in their highly metastatic derivative cell lines, KM12SM and KM12L4A. Activity was assessed by reactivity with a phospho-specific antibody raised against the region of c-Src containing tyrosine-416, the presumed site of autophosphorylation. (B) Comparison of paxillin tyrosine phosphorylation in KM12C and KM12L4A cells. Paxillin was immunoprecipitated, blotted and probed with phosphotyrosine-specific antibodies (upper panel) or anti-paxillin (lower panel).

Mentions: Most of the molecular studies on Src family kinases (SFKs) have been carried out in fibroblasts. Consequently, much less is known about SFK function in epithelial cells that are the targets of cancerous transformation in humans. We set out to address how elevated c-Src contributes to the behaviour of colon cancer cells, specifically examining cell growth and adhesion to extracellular matrix components. For these experiments we used cell lines from the Fidler model of colorectal metastasis (Morikawa et al, 1988). In this model, cells that have low intrinsic capacity to metastasise to the liver after intrasplenic injection (KM12C) were compared with derivative cell lines that have much greater metastatic capacity in this assay (KM12SM and KM12L4A). The generation and characterisation of these cell lines has been described (Morikawa et al, 1988). Importantly, we confirmed that the actual cells we used in our studies retained the characteristics of originally reported Fidler cell lines with respect to metastatic capacity (not shown), and the acquisition of metastatic potential correlated with elevated c-Src expression (Figure 1AFigure 1


Elevated c-Src is linked to altered cell-matrix adhesion rather than proliferation in KM12C human colorectal cancer cells.

Jones RJ, Avizienyte E, Wyke AW, Owens DW, Brunton VG, Frame MC - Br. J. Cancer (2002)

(A) Immunoblots showing expression (upper panel) and activity (lower panel) of c-Src in the poorly metastatic cell line, KM12C, and in their highly metastatic derivative cell lines, KM12SM and KM12L4A. Activity was assessed by reactivity with a phospho-specific antibody raised against the region of c-Src containing tyrosine-416, the presumed site of autophosphorylation. (B) Comparison of paxillin tyrosine phosphorylation in KM12C and KM12L4A cells. Paxillin was immunoprecipitated, blotted and probed with phosphotyrosine-specific antibodies (upper panel) or anti-paxillin (lower panel).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2376185&req=5

fig1: (A) Immunoblots showing expression (upper panel) and activity (lower panel) of c-Src in the poorly metastatic cell line, KM12C, and in their highly metastatic derivative cell lines, KM12SM and KM12L4A. Activity was assessed by reactivity with a phospho-specific antibody raised against the region of c-Src containing tyrosine-416, the presumed site of autophosphorylation. (B) Comparison of paxillin tyrosine phosphorylation in KM12C and KM12L4A cells. Paxillin was immunoprecipitated, blotted and probed with phosphotyrosine-specific antibodies (upper panel) or anti-paxillin (lower panel).
Mentions: Most of the molecular studies on Src family kinases (SFKs) have been carried out in fibroblasts. Consequently, much less is known about SFK function in epithelial cells that are the targets of cancerous transformation in humans. We set out to address how elevated c-Src contributes to the behaviour of colon cancer cells, specifically examining cell growth and adhesion to extracellular matrix components. For these experiments we used cell lines from the Fidler model of colorectal metastasis (Morikawa et al, 1988). In this model, cells that have low intrinsic capacity to metastasise to the liver after intrasplenic injection (KM12C) were compared with derivative cell lines that have much greater metastatic capacity in this assay (KM12SM and KM12L4A). The generation and characterisation of these cell lines has been described (Morikawa et al, 1988). Importantly, we confirmed that the actual cells we used in our studies retained the characteristics of originally reported Fidler cell lines with respect to metastatic capacity (not shown), and the acquisition of metastatic potential correlated with elevated c-Src expression (Figure 1AFigure 1

Bottom Line: Elevated expression and/or activity of c-Src, the prototype of the Src family of protein tyrosine kinases, is associated with the development of human colon cancer.Although elevated Src correlates with ability to metastasise to the liver after intrasplenic injection, we found that this was not linked to enhanced growth, either in vitro or in vivo as sub-cutaneous tumours.However, elevated Src was associated with enhanced attachment to extracellular matrix.

View Article: PubMed Central - PubMed

Affiliation: Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, Scotland, UK.

Show MeSH
Related in: MedlinePlus