Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China.
Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China.
Int J Biol Sci. 2021 Feb 17;17(3):848-860. doi: 10.7150/ijbs.53657. eCollection 2021.
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 and . 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.
CD151 在不同癌症中影响多种信号通路，并通过尚未明确的机制促进结直肠癌（CRC）细胞的恶性转化。本研究旨在全面评估 CD151 在 CRC 中的功能。组织微阵列分析显示，CRC 组织和细胞中的 CD151 水平明显高于对照组。CD151 下调抑制 CRC 细胞的活力、迁移和侵袭。同样，CD151 沉默抑制了小鼠异种移植物的生长。RNA-seq 显示，在培养的 CRC 细胞和异种移植物中，CD151 敲低显著改变了多个基因。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）和富含亮氨酸重复的 G 蛋白偶联受体 5（LGR5）与 CD151 一起被下调。免疫共沉淀和质谱结果通过 qRT-PCR 和免疫印迹进行了验证。此外，下拉实验和免疫荧光证实了 TGFβ1、CEACAM6 和 LGR5 与 CD151 的关联。本研究表明，CD151 沉默可能通过 TGFβ1 调节抑制 CEACAM6、LGR5 和 Wnt 通路，为 CD151 在结直肠癌发生中的作用提供了全面的认识。我们的研究结果为 CD151 参与 CRC 致癌的信号网络提供了深入了解，这可能有助于设计针对 CD151 信号的新型靶向治疗方法，用于治疗 CRC。
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