Toggle Main Menu Toggle Search

Open Access padlockePrints

Activation of cellular invasion by trefoil peptides and src is mediated by cyclooxygenase- and thromboxane A2 receptor-dependent signaling pathways

Lookup NU author(s): Professor Bruce Westley, Dr Felicity May


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


We have investigated the possible functional relationships between cellular invasion pathways induced by trefoil factors (TFFs), src, and the cyclooxygenases COX-1 and COX-2. Pharmacological inhibitors of the Rho small GTPase (C3 exoenzyme), phospholipase C (U-73122), cyclooxygenases (SC-560, NS-398), and the thromboxane A2 receptor (TXA2-R) antagonist SQ-295 completely abolished invasion induced by intestinal trefoil factor, pS2, and src in kidney and colonic epithelial cells MDCKts.src and PCmsrc. In contrast, invasion was induced by the TXA2-R mimetic U-46619, constitutively activated forms of the heterotrimeric G-proteins G alphaq (AG alphaq), G alpha 12, G alpha 13 (AG alpha 12/13), which are signaling elements downstream of TXA2-R. Ectopic overexpression of pS2 cDNA and protein in MDCKts.src-pS2 cells and human colorectal cancer cells HCT8/S11-pS2 initiate distinct invasion signals that are Rho independent and COX and TXA2-R dependent. We detected a marked induction of COX-2 protein and accumulation of the stable PGH2/TXA2 metabolite TXB2 in the conditioned medium from cells transformed by src. This led to activation of the TXA2R-dependent invasion pathway, which is monitored via a Rho- and G alpha 12/G alpha 13-independent mechanism using the G alphaq/PKC signaling cascade. These findings identify a new intracrine/paracrine loop that can be monitored by TFFs and src in inflammatory diseases and progression of colorectal cancers.

Publication metadata

Author(s): Rodrigues S, Nguyen QD, Faivre S, Bruyneel E, Thim L, Westley B, May F, Flatau G, Mareel M, Gespach C, Emami S

Publication type: Article

Publication status: Published

Journal: The FASEB Journal

Year: 2001

Volume: 15

Issue: 9

Pages: 1517-1528

ISSN (print): 0892-6638

ISSN (electronic): 1530-6860

Publisher: Federation of American Societies for Experimental Biology


DOI: 10.1096/fj.00-0802com


Altmetrics provided by Altmetric