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Induction of scattering and cellular invasion by trefoil peptides in src- and RhoA-transformed kidney and colonic

S Emami1, N Le Floch, E Bruyneel

  • 1INSERM U482, Signal Transduction and Cellular Functions in Diabetes and Digestive Cancers, Hôpital Saint-Antoine, 75571 Paris Cedex 12, France.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|February 7, 2001
PubMed

Insights

Trefoil factors (TFFs) promote epithelial healing but can drive colon cancer invasion. Activated src and RhoA pathways enable TFF-induced invasion, suggesting TFFs as potential colon cancer targets.

Area of Science:

  • Gastroenterology
  • Oncology
  • Molecular Biology

Background:

  • Trefoil factors (TFFs) are peptides crucial for gastrointestinal mucosal healing.
  • The precise molecular mechanisms of TFF action and their role in cancer progression remain largely unknown.

Purpose of the Study:

  • To investigate the role of TFFs in epithelial cell invasion and their potential involvement in colorectal cancer progression.

Main Methods:

  • Utilized premalignant and transformed epithelial cell lines (PC/AA/C1, MDCK, HCT8/S11) to assess TFF-mediated invasion and scattering.
  • Investigated the involvement of signaling pathways (src, RhoA, PI3K, PLC, PKC, TOR) in TFF-induced cellular responses.
  • Analyzed TFF expression in human colorectal tumors and adjacent mucosa using Western blot and immunohistochemistry.

Main Results:

  • Exogenous TFFs did not induce invasion in premalignant cells, but activated src and RhoA enabled TFF-mediated invasion and cell scattering.
  • Stable expression of pS2 (a TFF) promoted constitutive invasiveness in transformed cells.
  • TFF-mediated invasion involved signaling pathways like PI3K, PLC, PKC, and TOR.
  • Intense pS2 expression was observed in human colorectal tumors, correlating with neoplastic progression.

Conclusions:

  • TFFs can contribute to colon cancer cell scattering and invasion, potentially through autocrine mechanisms.
  • TFFs represent promising therapeutic targets for controlling colon cancer progression.

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