Carcinogenesis：陈雁等发现一个新的结肠癌抑癌基因PAQR3

近日，国际肿瘤领域知名杂志Carcinogenesis发表了中科院上海生命科学研究院营养科学研究所陈雁研究组的最新研究进展，揭示了PAQR3是结肠癌发生过程中的一个新的抑癌基因。

陈雁研究组长期致力于PAQR3即RKTG的研究，发现PAQR3能通过在空间上调控细胞内关键信号通路，影响多种细胞功能，但是关于PAQR3是否在结肠癌中发挥作用还不清楚。

在这一研究中，博士生王笑等人发现，PAQR3基因缺失能够促进一种可以自发形成肠癌的APCmin小鼠的肿瘤形成，PAQR3基因缺失显著增加了小鼠的肠肿瘤数量。在结肠癌细胞系中，研究人员发现PAQR3负向调控细胞增殖以及EGF介导的细胞信号通路的转导。通过与营养所方靖研究组合作研究发现，在中国人结肠癌患者的临床样本中，PAQR3的表达水平在肿瘤中显著低于癌旁组织，并且PAQR3的表达水平与肿瘤恶性程度呈负相关。

因此，这一工作在细胞、动物和人群三个层面上揭示了PAQR3是一个参与结肠癌发生发展的抑癌基因，为未来结肠癌的治疗提供了一个新的潜在靶点。

该研究得到中科院、基金委和科技部项目的支持。

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.