Aberrant activation of c-kit protects colon carcinoma cells against apoptosis and enhances their invasive potential

G. Bellone, A. Carbone, N. Sibona, O. Bosco, D. Tibaudi, C. Smirne, T. Martone, C. Gramigni, M. Camandona, G. Emanuelli, U. Rodeck

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Abstract

Multiple genetic aberrations contribute to the development of biologically aggressive, clinically malignant colorectal carcinomas (CRCs). Some of these have been linked to inappropriate signaling through the tyrosine kinase moieties of growth factor receptors. We have described previously (G. Bellone et al., J. Cell. Physiol., 172: 1-11, 1997) that human CRCs overexpress both the receptor tyrosine kinase c-kit and its ligand, stem cell factor (SCF), relative to normal mucosa cells, thus establishing an autocrine c-kit-mediated loop. In addition, we noted that exogenous SCF contributes to anchorage-independent growth of HT-29 colon carcinoma cells in semisolid medium. Here, we investigated possible roles of the c-kit/SCF autocrine/paracrine system in survival and invasive capacity of DLD-1 colon carcinoma cells. We report that SCF was required for migration and invasion of DLD-1 cells through reconstituted basement membranes (Matrigel) and up-regulated gelatinase (matrix metalloproteinase-9) activity in DLD-1 cells. Furthermore, we describe that SCF supported survival of DLD-1 cells in growth factor-deprived conditions. These results suggest multiple roles of c-kit activation in support of the malignant phenotype of DLD-1 cells related to growth, survival, migration, and invasive potential.

Original languageEnglish
Pages (from-to)2200-2206
Number of pages7
JournalCancer Research
Volume61
Issue number5
Publication statusPublished - Mar 1 2001

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bellone, G., Carbone, A., Sibona, N., Bosco, O., Tibaudi, D., Smirne, C., Martone, T., Gramigni, C., Camandona, M., Emanuelli, G., & Rodeck, U. (2001). Aberrant activation of c-kit protects colon carcinoma cells against apoptosis and enhances their invasive potential. Cancer Research, 61(5), 2200-2206.