Chitinase 3-like 1-CD44 interaction promotes metastasis and epithelial-to-mesenchymal transition through β-catenin/Erk/Akt signaling in gastric cancer

Journal of Experimental & Clinical Cancer Research : CR
Biao GengQiang You

Abstract

Enzymatically inactive chitinase-like protein CHI3L1 drives inflammatory response and promotes tumor progression. However, its role in gastric cancer (GC) tumorigenesis and metastasis has not yet been fully elucidated. We determined the significance of CHI3L1 expression in patients with GC. We also explored an as-yet unknown receptor of CHI3L1 and investigated the involved signaling in GC metastasis. CHI3L1 expression was evaluated by immunoblotting, tissue microarray-based immunohistochemistry analysis (n = 100), and enzyme linked immunosorbent assay (ELISA) (n = 150). The interactions between CD44 and CHI3L1 or Interleukin-13 receptor alpha 2 (IL-13Rα2) were analyzed by co-immunoprecipitation, immunofluorescence co-localization assay, ELISA, and bio-layer interferometry. The roles of CHI3L1/CD44 axis in GC metastasis were investigated in GC cell lines and experimental animal model by gain and loss of function. CHI3L1 upregulation occurred during GC development, and positively correlated with GC invasion depth, lymph node status, and tumor staging. Mechanically, CHI3L1 binding to CD44 activated Erk and Akt, along with β-catenin signaling by phosphorylating β-catenin at Ser552 and Ser675. CD44 also interacted with IL-13Rα2 to f...Continue Reading

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Citations

Feb 12, 2020·Reviews in the Neurosciences·Valentin DichevVictoria Sarafian
Aug 30, 2020·Journal of Experimental & Clinical Cancer Research : CR·Xiang LiQiang You
Feb 19, 2020·Journal of Neuroinflammation·Marta Moreno-RodriguezElliott J Mufson
Sep 16, 2020·Signal Transduction and Targeted Therapy·Ting ZhaoQiang You
Dec 10, 2020·Neurology. Neuroimmunology and Neuroinflammation·Rucsanda PinteacManuel Comabella
Sep 17, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Dan HøgdallJesper B Andersen
Jan 17, 2021·International Journal of Molecular Sciences·Xujun SongMarko Kornmann
Apr 14, 2021·Scientific Reports·Valentin CaluLiviu Bilteanu
Apr 24, 2021·Proceedings of the National Academy of Sciences of the United States of America·Norihisa NishimuraPatrizia Farci
May 1, 2021·International Journal of Molecular Sciences·Gustavo Ramos-EspinosaChristian Gorzelanny
Aug 28, 2021·Cancers·Yen-Yun WangShyng-Shiou F Yuan
Aug 31, 2021·Clinical and Translational Medicine·Chao WangWenxian Guan
Nov 2, 2021·The Journal of Clinical Investigation·Bing MaJack A Elias
Jul 22, 2021·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Weifeng XuXiaobing Chen

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Methods Mentioned

BETA
co-immunoprecipitation
ELISA
biolayer interferometry
electrophoresis
biosensor
Assay
lavage
co-IP
confocal microscopy
xenograft

Software Mentioned

ForteBio Data Analysis
SPSS
GraphPad Prism

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