التفاصيل البيبلوغرافية
| العنوان: |
Muscarinic receptor agonists stimulate human colon cancer cell migration and invasion. |
| المؤلفون: |
Belo, Angelica, Kunrong Cheng, Chahdi, Ahmed, Shant, Jasleen, Guofeng Xie, Khurana, Sandeep, Raufman, Jean-Pierre |
| المصدر: |
American Journal of Physiology: Gastrointestinal & Liver Physiology; May2011, Vol. 300, pG749-G760, 12p |
| مصطلحات موضوعية: |
COLON cancer, METASTASIS, EPIDERMAL growth factor, CELL migration, METALLOPROTEINASES, ATROPINE |
| مستخلص: |
Muscarinic receptors (CHRM) are overexpressed in colon cancer. To explore a role for muscarinic receptor signaling in colon cancer metastasis, we used human H508 and HT29 colon cancer cells that coexpress epidermal growth factor (ERBB) and CHRM3 receptors. In a wound closure model, following 8-h incubation of H508 cells with 100 μM ACh we observed a threefold increase in cell migration indistinguishable from the actions of epidermal growth factor (EGF). Atropine blocked the actions of ACh but not of EGF. In SNU-C4 colon cancer cells that express ERBB but not CHRM, EGF caused a threefold increase in migration; ACh had no effect. ACh-induced cell migration was attenuated by chemical inhibitors of ERBB1 activation, by anti-ERBB1 antibody, and by inhibitors of ERK and phosphatidylinositol 3-kinase (PI3K) signaling. Consistent with matrix metalloproteinase-7 (MMP7)-mediated release of an ERBB1 ligand, heparin binding epidermal growth factor-like growth factor (HBEGF), ACh-induced migration was inhibited by an MMP inhibitor and by anti-MMP7 and -HBEGF antibodies. ACh-induced cell migration was blocked by inhibiting RhoA and ROCK, key proteins that interact with the actin cytoskeleton. ACh-induced RhoA activation was attenuated by agents that inhibit ERBB1, ERK, and PI3K activation. Collectively, these findings indicate that ACh-induced cell migration is mediated by MMP7-mediated release of HBEGF, an ERBB ligand that activates ERBB1 and downstream ERK and PI3K signaling. In a cell invasion model, ACh-induced HT29 cell invasion was blocked by atropine. In concert with previous observations, these findings indicate that muscarinic receptor signaling plays a key role in colon cancer cell proliferation, survival, migration, and invasion. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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