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PYGB facilitates cell proliferation and invasiveness in non-small cell lung cancer by activating the Wnt–β-catenin signaling pathway

2020· article· en· 39 citations· W3011497090 on OpenAlex· 10.1139/bcb-2019-0445

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Canadian venueIt was published in a Canadian venue.

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Abstract

Brain-type glycogen phosphorylase (PYGB) has been correlated with the progression of various human malignancies; however, its effects and regulatory mechanisms in non-small cell lung cancer (NSCLC) are still unclear. We used Western blotting, immunohistochemistry, and qRT-PCR to verify that the protein and mRNA expression levels of PYGB are up-regulated in both NSCLC cell lines and tissues. The expression of PYGB was positively related to TNM stage, positive lymph node metastasis, and poor prognosis in patients with NSCLC. Moreover, overexpression of PYGB promoted cell proliferation, migration, and invasiveness, but inhibited apoptosis, in vitro. Immunofluorescence assays showed that overexpression of PYGB promoted the nuclear import and accumulation of β-catenin. By comparison, silencing PYGB produced the opposite effects. Further, overexpression of PYGB resulted in activation of the Wnt signaling pathway, and transfection with Sh-PYGB produced the opposite effect, and these effects were abrogated by XAV-939 (a β-catenin inhibitor) or overexpression of β-catenin, respectively. Finally, knockdown of PYGB inhibited tumor growth in a mouse model of xenograft tumors. These findings highlight the role of PYGB in the progression of NSCLC, and reveal a link between PYGB and the Wnt-β-catenin signaling pathway, thus providing a new potential target for treatment of NSCLC.

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The record

Venue
Biochemistry and Cell Biology
Topic
Wnt/β-catenin signaling in development and cancer
Field
Biochemistry, Genetics and Molecular Biology
Canadian institutions
Funders
Keywords
Wnt signaling pathwayCell growthCell biologySignal transductionCellCateninBiologyCancer researchLung cancerChemistryPathologyBiochemistryMedicine
Has abstract in OpenAlex
yes