Int J Biol Sci 2021; 17(3):848-860. doi:10.7150/ijbs.53657

Research Paper

CD151 promotes Colorectal Cancer progression by a crosstalk involving CEACAM6, LGR5 and Wnt signaling via TGFβ1

Tao Yang1#, Huibing Wang2#, Meng Li2, Linqi Yang2, Yu Han3, Chao Liu4, Baowen Zhang5, Mingfa Wu6, Gang Wang7, Zhenya Zhang8, Wenqi Zhang9, Jianming Huang1, Huaxing Zhang10, Ting Cao1, Pingping Chen2✉, Wei Zhang2✉

1. Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China.
2. Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China.
3. Department of Pharmacy, Children's Hospital of Hebei Province, Shijiazhuang, Hebei, 050000, China.
4. Department of Laboratory Animal Science, Hebei Key Lab of Hebei Laboratory Animal Science, Hebei Medical University, Shijiazhuang, Hebei, 050017, China.
5. Hebei Collaboration Innovation Center for Cell Signaling, Key Laboratory of Molecular and Cellular Biology of Ministry of Education, Hebei Key Laboratory of Moleculor and Cellular Biology, College of Life Sciences, Hebei Normal University, Shijiazhuang, Hebei, 050024, China.
6. Department of Gastrointestinal Surgery, Dingzhou City People's Hospital, Dingzhou, Hebei, 073000, China.
7. Department of Third General Surgery, Cangzhou City People's Hospital, Cangzhou, Hebei, 061000, China.
8. Department of Second General Surgery, Hebei Medical University Fourth hospital, Shijiazhuang, Hebei, 050011, China.
9. College of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei, 500017, China.
10. School of Basic Medical Sciences, Hebei Medical University, Shijiazhuang 050017, Hebei, China.
#These authors contributed equally to this work.

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Citation:
Yang T, Wang H, Li M, Yang L, Han Y, Liu C, Zhang B, Wu M, Wang G, Zhang Z, Zhang W, Huang J, Zhang H, Cao T, Chen P, Zhang W. CD151 promotes Colorectal Cancer progression by a crosstalk involving CEACAM6, LGR5 and Wnt signaling via TGFβ1. Int J Biol Sci 2021; 17(3):848-860. doi:10.7150/ijbs.53657. Available from https://www.ijbs.com/v17p0848.htm

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Abstract

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.

Keywords: CD151, TGFβ1, LGR5, CEACAM6, Wnt signaling, colorectal cancer