CD151 impacts various signaling pathways in different cancers, and promotes colorectal cancer (CRC) cell malignancy by yet undefined mechanisms. This study aimed to comprehensively assess CD151's function in CRC. CD151 levels were significantly higher in CRC tissues and cells compared with controls in the tissue microarray. Cell viability, migration and invasion were suppressed by CD151 downregulation in CRC cells. Consistently, mouse xenografts were inhibited by CD151 silencing. RNA-seq revealed that multiple genes were significantly altered by CD151 knockdown in cultured CRC cells and xenografts. Particularly, transforming growth factor β1 (TGFβ1), carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) alongside CD151 were downregulated both in vitro and in vivo. Co-immunoprecipitation and mass spectrometry results were validated by qRT-PCR and immunoblot. Moreover, pull-down assay and immunofluorescence confirmed the associations of TGFβ1, CEACAM6 and LGR5 with CD151. This study demonstrated CEACAM6, LGR5 and Wnt pathway suppression by CD151 silencing might occur through TGFβ1 regulation, offering a comprehensive view of CD151's roles in colorectal carcinogenesis. Our findings provide an insight into the CD151-involved signaling network in CRC oncogenesis, which could be utilized to design novel targeted therapies against CD151-based signaling in treatment for CRC.

中文翻译：

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CD151 通过 TGFβ1 涉及 CEACAM6、LGR5 和 Wnt 信号传导的串扰促进结直肠癌进展

CD151 影响不同癌症中的各种信号通路，并通过尚未明确的机制促进结直肠癌 (CRC) 细胞恶性肿瘤。本研究旨在全面评估CD151在CRC中的功能。与组织微阵列中的对照相比，CRC 组织和细胞中的 CD151 水平显着较高。CRC 细胞中 CD151 下调可抑制细胞活力、迁移和侵袭。一致地，小鼠异种移植物受到 CD151 沉默的抑制。RNA-seq 显示，在培养的 CRC 细胞和异种移植物中，CD151 敲低显着改变了多个基因。特别是，转化生长因子 β1 (TGFβ1)、癌胚抗原相关细胞粘附分子 6 (CEACAM6) 和富含亮氨酸重复序列的 G 蛋白偶联受体 5 (LGR5) 以及 CD151 均被下调体外和体内。通过 qRT-PCR 和免疫印迹验证了免疫共沉淀和质谱结果。此外，pull-down 测定和免疫荧光证实了 TGFβ1、CEACAM6 和 LGR5 与 CD151 的关联。这项研究证明 CD151 沉默可能通过 TGFβ1 调节来抑制 CEACAM6、LGR5 和 Wnt 通路，从而全面了解 CD151 在结直肠癌发生中的作用。我们的研究结果提供了对 CRC 肿瘤发生中 CD151 相关信号网络的深入了解，可用于设计针对 CRC 治疗中基于 CD151 的信号传导的新型靶向疗法。