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Pasteurella Multocida Toxin Mediated ECM Expression Is Independent of mTOR signaling pathway
Author(s) -
Oubrahim Hammou,
Leong Megan,
Chock Boon P
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb151
Subject(s) - microbiology and biotechnology , biology , signal transduction , pi3k/akt/mtor pathway , autocrine signalling , mapk/erk pathway , paracrine signalling , cell culture , receptor , genetics , biochemistry
Bacterial virulence factors that interfere with cell signaling and result in disruption of normal cell division and apoptosis could facilitate cancer metastasis via unknown mechanisms. Pasteurella multocida toxin (PMT) is an intracellular acting bacterial protein known for its potent mitogenic properties in vitro and in vivo and its ability to induce strong anchorage‐independent growth for certain type of cells. These properties suggest that PMT might have the potential to act as a tumor promoter especially in the case of chronic infections. We have shown that rPMT induces cell proliferation in serum‐starved Swiss 3T3 cells by hijacking cellular signal transduction pathways via deamidation of heterotrimeric G‐proteins and leads to a sustained activation of mTOR, MAPK, and membrane associated tyrosine kinase signaling. In addition, further experiments revealed that PMT induced a prolonged upregulation of chromosomal passenger complex (CPC) proteins including survivin and aurora kinase B both at mRNA and protein levels in serum starved Swiss 3T3 cells treated with PMT in a manner dependent on both mTOR and MAPK signaling pathways. An increasing body of evidence supports the idea that extracellular matrix (ECM) proteins are major players in the global control of intercellular communication and integration of environmental signals. It was not known whether rPMT‐treated cells are able to express and secrete into the medium a substrate(s) capable of activating autocrine and/or paracrine signaling. Microarray analysis identified connective tissue growth factor (CTGF) mRNA as the most upregulated gene in 3T3 cells, along with other genes involved in cell proliferation and cancer biology. The elevation of CTGF, along with other extracellular matrix proteins, were confirmed by RT‐PCR and Western blot analysis. In accord with rPMT‐induced mTOR activation, upregulation of CTGF was mediated by deamidation of Gα q/11, and was independent of TGFβ, a well‐known inducer of CTGF. However, PMT‐induced ECM expression is independent of both mTOR, MAPK and membrane associated tyrosine kinase activation. Taken together, our results show that PMT activates mTOR and membrane associated tyrosine kinase, and MAPK leading to the upregulation of proteins involved in cell proliferation but do not have any effect on the expression of ECM proteins. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .