These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: FAPalpha, a surface peptidase expressed during wound healing, is a tumor suppressor.
    Author: Ramirez-Montagut T, Blachere NE, Sviderskaya EV, Bennett DC, Rettig WJ, Garin-Chesa P, Houghton AN.
    Journal: Oncogene; 2004 Jul 15; 23(32):5435-46. PubMed ID: 15133496.
    Abstract:
    Fibroblast activation protein-alpha (FAP) is a cell surface serine protease expressed at sites of tissue remodeling in embryonic development. FAP is not expressed by mature somatic tissues except activated melanocytes and fibroblasts in wound healing or tumor stroma. FAP expression is specifically silenced in proliferating melanocytic cells during malignant transformation. To study the role of FAP as a tumor suppressor, the gene for mouse fap was cloned and mutated at the catalytic domain (FAP serine mutant, FSM). We found that expression of FAP or FSM at physiologic levels in mouse melanoma cells abrogated tumorigenicity. Remarkably, the mutant form FSM lacking specific serine protease activity was a more potent tumor suppressor. Tumor rejection was not due to adaptive immune responses because RAG1-/- mice challenged with melanoma cells expressing either FAP or FSM were not tumorigenic. In in vitro assays, FAP or FSM expression restored contact inhibition, led to cell cycle arrest at G0/G1 phase, and increased susceptibility to stress-induced apoptosis. Cell death in FAP+ or FSM+ melanoma cells was readily triggered by depletion of survival factors from the media, leading to subsequent activation of caspases via the intrinsic pathway. These results show that expression of FAP is a tumor suppressor that abrogates tumorigenicity through regulation of cell growth and survival.
    [Abstract] [Full Text] [Related] [New Search]