PLOD2 regulated by transcription factor FOXA1 promotes metastasis in NSCLC

Cell Death & Disease
Hongzhi DuLi Sun

Abstract

In multiple types of tumors, fibrotic collagen is regarded as the 'highway' for cancer cell migration, which is mainly modified by lysyl hydroxylase 2 (PLOD2). The previous findings have demonstrated that the expression of PLOD2 was regulated by multiple factors, including HIF-1α, TGF-β and microRNA-26a/b. Although PLOD2 was confirmed to be related to poor prognosis in lung adenocarcinoma, the regulatory mechanism and function of PLOD2 in human lung adenocarcinoma is poorly understood. On the other hand, upregulation or hyperactivation of epidermal growth factor receptor is considered as a prognostic marker in many cancers, especially in non-small-cell lung cancer (NSCLC). In this study, we found that PLOD2 was elevated in NSCLC specimens and positively links to NSCLC poor prognosis. Gain- and loss-of-function studies and orthotopic implantation metastasis model pinpointed that PLOD2 promotes NSCLC metastasis directly by enhancing migration and indirectly by inducing collagen reorganization. In addition, we revealed that PLOD2 was regulated by PI3K/AKT-FOXA1 axis. The transcription factor FOXA1 directly bound to the PLOD2 promoter, and turned on PLOD2 transcription. In summary, our findings revealed a regulatory mechanism of NS...Continue Reading

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Sep 29, 2020·Cancer Medicine·Anders BerglundJong Y Park
Jul 14, 2018·Frontiers in Cell and Developmental Biology·Yifei Qi, Ren Xu
Nov 20, 2019·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Wenwu DuYi He
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Oct 6, 2020·Frontiers in Oncology·Amelia L Parker, Thomas R Cox

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Methods Mentioned

BETA
immunoprecipitation
nuclear translocation
ChIP
reverse transcription-PCR
biopsies
transfection
Assay
xenograft

Software Mentioned

Mapviewer
Image
KM
KM plotter
Pro Plus
GraphPad Prism
Ensemble

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