近日,，國際腫瘤領(lǐng)域知名雜志Carcinogenesis發(fā)表了中科院上海生命科學研究院營養(yǎng)科學研究所陳雁研究組的最新研究進展,，揭示了PAQR3是結(jié)腸癌發(fā)生過程中的一個新的抑癌基因。
陳雁研究組長期致力于PAQR3即RKTG的研究,，發(fā)現(xiàn)PAQR3能通過在空間上調(diào)控細胞內(nèi)關(guān)鍵信號通路,，影響多種細胞功能，但是關(guān)于PAQR3是否在結(jié)腸癌中發(fā)揮作用還不清楚,。
在這一研究中，博士生王笑等人發(fā)現(xiàn),，PAQR3基因缺失能夠促進一種可以自發(fā)形成腸癌的APCmin小鼠的腫瘤形成,，PAQR3基因缺失顯著增加了小鼠的腸腫瘤數(shù)量。在結(jié)腸癌細胞系中,，研究人員發(fā)現(xiàn)PAQR3負向調(diào)控細胞增殖以及EGF介導的細胞信號通路的轉(zhuǎn)導,。通過與營養(yǎng)所方靖研究組合作研究發(fā)現(xiàn)，在中國人結(jié)腸癌患者的臨床樣本中,，PAQR3的表達水平在腫瘤中顯著低于癌旁組織,，并且PAQR3的表達水平與腫瘤惡性程度呈負相關(guān)。
因此,，這一工作在細胞,、動物和人群三個層面上揭示了PAQR3是一個參與結(jié)腸癌發(fā)生發(fā)展的抑癌基因，為未來結(jié)腸癌的治療提供了一個新的潛在靶點,。
該研究得到中科院,、基金委和科技部項目的支持。（生物谷Bioon.com）
doi:10.1093/carcin/bgs245
PMC:
PMID:
PAQR3 plays a suppressive role in the tumorigenesis of colorectal cancers
Xiao Wang1, Xue-bing Li1, Fengjuan Fan1, Shi Jiao1, Lingdi Wang1, Lu Zhu1, Yi Pan1, Guo-hao Wu2, Zhi-Qiang LING3, jing Fang1,* and Yan Chen1,*
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 ApcMin/+ mice that have a germ-line mutation of the gene encoding tumor suppressor adenomatous polyposis coli (APC). The survival time and tumor area in the small intestine of the ApcMin/+ mice was significantly aggravated by Paqr3 deletion. The cell proliferation rate, anchorage-independent growth, EGF-stimulated ERK phosphorylation, and EGF-induced nuclear accumulation of b-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.
