application) Anchorage-independent growth is a hallmark of cancer cells in general. Growth factors and the extracellular matrix coordinately mediate anchorage-dependent proliferation. Growth factor and integrin receptors transduce signals from soluble growth factors and insoluble extracellular matrix proteins, respectively. The signaling pathways for growth factor receptors and integrins converge at several levels within cells, but how their signaling pathways are integrated is not entirely clear. During colonic tumorigenesis, integrin expression is greatly diminished, and the specific loss of alpha 5/beta I integrin heterodimer expression has been observed in vivo. Transfection of alpha 5 integrin into malignant CHO and HT-29 colon cancer cells devoid of alpha 5/beta I integrin expression abrogates the malignant phenotype and inhibits their proliferation in the absence of fibronectin. It has been recently demonstrated that P1 integrins can activate the epidermal growth factor receptor (EGFR) in the presence of fibronectin. This integrin-mediated EGFR activation is necessary for cell survival in the absence of cell adhesion and proliferation. Thus, we hypothesize that expression of alpha 5101 integrin in colon cancer cell lines lacking alpha 51P1 integrin expression, renders them dependent on fibronectin-induced EGFR activation for anchorage-dependent growth and anchorage-independent survival and/or proliferation. The demonstration of a direct modulation of EGFR- mediated cell growth by a single integrin would expand our knowledge of how colon cancer cells escape anchorage-dependent growth controls and might lead to novel therapeutic strategies for colon cancer.
| Kuwada, Scott K; Scaife, Courtney L; Kuang, Jinqiu et al. (2004) Effects of trastuzumab on epidermal growth factor receptor-dependent and -independent human colon cancer cells. Int J Cancer 109:291-301 |
| Scaife, Courtney L; Kuang, Jinqiu; Wills, Jason C et al. (2002) Nuclear factor kappaB inhibitors induce adhesion-dependent colon cancer apoptosis: implications for metastasis. Cancer Res 62:6870-8 |
