title: PAQR3 plays a suppressive role in the tumorigenesis of colorectal cancers.
abstract: PAQR3 is a member of the progestin and adipoQ receptor (PAQR) family and was recently characterized as a spatial regulator that negatively modulates Ras/Raf/MEK/ERK signaling cascade. However, little is known about the physiological functions of PAQR3 in the tumorigenesis of colorectal cancers. The function of PAQR3 in colorectal cancer development in mice was analyzed by crossing Paqr3-depleted mice with Apc(Min/+) mice that have a germline mutation of the gene-encoding tumor suppressor adenomatous polyposis coli (APC). The survival time and tumor area in the small intestine of the Apc(Min/+) mice was significantly aggravated by Paqr3 deletion. The cell proliferation rate, anchorage-independent growth, EGF-stimulated ERK phosphorylation and EGF-induced nuclear accumulation of β-catenin were inhibited by PAQR3 overexpression and enhanced by PAQR3 knockdown in SW-480 colorectal cancer cells. In humans, the expression level of PAQR3 was significantly decreased in colorectal cancer samples in comparison with adjacent normal tissues. In addition, the expression level of PAQR3 was inversely associated with tumor grade in the colorectal cancer samples. Collectively, our data reveal for the first time that PAQR3 has a tumor suppressor activity in the development of colorectal cancers.
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai China.
authors: Xiao
authors: X
authors: Wang
authors: Xuebing
authors: X
authors: Li
authors: Fengjuan
authors: F
authors: Fan
authors: Shi
authors: S
authors: Jiao
authors: Lingdi
authors: L
authors: Wang
authors: Lu
authors: L
authors: Zhu
authors: Yi
authors: Y
authors: Pan
authors: Guohao
authors: G
authors: Wu
authors: Zhi-Qiang
authors: ZQ
authors: Ling
authors: Jing
authors: J
authors: Fang
authors: Yan
authors: Y
authors: Chen
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000502:physiology*; D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010766:Phosphorylation / Q000187:drug effects; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011980:Receptors, Progesterone / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D051176:beta Catenin; D004815:Epidermal Growth Factor