Diminished expression of CRHR2 in human colon cancer promotes tumor growth and EMT via persistent IL-6/Stat3 signaling (original) (raw)

Cellular and molecular gastroenterology and hepatology, 2015

Abstract

Chronic inflammation promotes development and progression of colorectal cancer (CRC). We explored the distribution of Corticotropin-Releasing-Hormone (CRH)-family of receptors and ligands in CRC and their contribution in tumor growth and oncogenic EMT. mRNA expression of CRH-family members was analyzed in CRC (N=56) and control (N=46) samples, 7 CRC cell lines and normal NCM460 cells. Immunohistochemical detection of CRHR2 was performed in 20 CRC and 5 normal tissues. Cell proliferation, migration and invasion were compared between Urocortin-2 (Ucn2)-stimulated parental and CRHR2-overexpressing (CRHR2+) cells in absence or presence of IL-6. CRHR2/Ucn2-targeted effects on tumor growth and EMT were validated in SW620-xenograft mouse models. CRC tissues and cell lines showed decreased mRNA and protein CRHR2 expression compared to controls and NCM460, respectively. The opposite trend was shown for Ucn2. CRHR2/Ucn2 signaling inhibited cell proliferation, migration, invasion and colony fo...

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