CXADR-Like膜蛋白（CLMP）与科萨奇病毒和腺病毒受体有结构上的关联。CLMP基因的致病变异已与先天性短肠综合征相关联，暗示了CLMP在肠道发育中的作用。然而，CLMP在调节肠道发育和稳态方面的贡献尚不清楚。本研究采用体内和体外的互补方法，包括具有可诱导的肠上皮细胞（IEC）特异性CLMP缺失的小鼠（ClmpΔIEC），肠器官样结构，过表达或缺失CLMP的IEC以及来自结直肠癌（CRC）患者的RNA测序数据，研究了CLMP在结肠上皮中的功能。CLMP的丧失增加了IEC的增殖，相反，CLMP的过表达减少了增殖。异种移植实验证明，在移植CLMP缺失的结肠肿瘤细胞的小鼠中，肿瘤生长增加，而移植CLMP过表达细胞的小鼠中观察到移植效果较差。在氮芥/硫酸葡聚糖诱导的结肠肿瘤发生模型中，ClmpΔIEC小鼠显示出加重的肿瘤负担，并且CLMP的表达在人类CRC样本中减少。机制研究揭示了CLMP调控IEC增殖与mTOR/Akt/β-连环素途径的信号传导有关。这些结果揭示了CLMP在结肠上皮中的新见解，强调了其在调节IEC增殖中的重要作用，表明在结直肠癌中具有抑制肿瘤的功能。AGA Institute 版权所有，Elsevier Inc.发表。

CXADR-Like Membrane Protein (CLMP) is structurally related to Coxsackie and Adenovirus Receptor. Pathogenic variants in CLMP gene have been associated with congenital short bowel syndrome, implying a role for CLMP in intestinal development. However, the contribution of CLMP to regulating gut development and homeostasis is unknown.In this study, we investigated CLMP function in the colonic epithelium using complementary in vivo and in vitro approaches including mice with inducible intestinal epithelial cell (IEC)-specific deletion of CLMP (ClmpΔIEC), intestinal organoids, IECs with overexpression or loss of CLMP and RNA-seq data from individuals with colorectal cancer (CRC).Loss of CLMP enhanced IEC proliferation and conversely, CLMP overexpression reduced proliferation. Xenograft experiments revealed increased tumor growth in mice implanted with CLMP-deficient colonic tumor cells, while poor engraftment was observed with CLMP-overexpressing cells. ClmpΔIEC mice showed exacerbated tumor burden in an Azoxymethane/Dextran Sulfate Sodium-induced colonic tumorigenesis model, and CLMP expression was reduced in human CRC samples. Mechanistic studies revealed that CLMP-dependent regulation of IEC proliferation is linked to signaling through mTOR/Akt/β-catenin pathways.These results reveal novel insights into CLMP function in the colonic epithelium, highlighting an important role in regulating IEC proliferation, suggesting tumor suppressive function in colon cancer.Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.