4.6 Article

Upregulated Collagen COL10A1 Remodels the Extracellular Matrix and Promotes Malignant Progression in Lung Adenocarcinoma

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FRONTIERS IN ONCOLOGY
卷 10, 期 -, 页码 -

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FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2020.573534

关键词

lung adenocarcinoma; DDR2; FAK; metastasis

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资金

  1. National Natural Science Foundation of China [81672294, 81702892]
  2. Project of Invigorating Health Care through Science, Technology Education, Jiangsu Provincial Medical Innovation Team [CXTDA2017002]
  3. Jiangsu Provincial key research development program [BE2017761]
  4. Foundation of Jiangsu Cancer hospital [ZK201601]
  5. young talents program of Jiangsu Cancer Hospital [23]
  6. Jiangsu Province Six Talent Peaks Project [WSN-027]

向作者/读者索取更多资源

Collagens are major components of the ECM in various organs, including the lungs. Ectopic expression of collagens can regulate the tumor progression and disease outcome through remodeling of the extracellular matrix (ECM). However, it remains largely unexplored whether collagens are involved in the tumor progression of lung adenocarcinoma (LUAD). Analysis of three LUAD transcriptional expression profiles showed that COL10A1 mRNA expression was up-regulated and associated with poor prognosis. Gain- and loss-of-function studies were performed to observe that up-regulated COL10A1 promotes LUAD cell proliferation and invasion in vitro and in vivo. In molecular mechanism study, we found that COL10A1 interacts with DDR2 and affects the downstream FAK signaling pathway to regulate LUAD cell progression. The expression of COL10A1 on tissue microarray (TMA) was also measured to explore the association between COL10A1 expression and patient outcome. The results addressed that COL10A1 is up-regulated and positively correlated with lymph node metastasis in lung adenocarcinoma, and the COL10A1 expression is also an independent prognostic factor. In summary, the up-regulated COL10A1 remodels the ECM and the COL10A1/DDR2/FAK axis regulates the proliferation and metastasis of LUAD cells, implying that COL10A1 is a promising therapeutic target and prognostic marker for LUAD patients.

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