Shanghai Medical College of Fudan University, Shanghai, 200032, People's Republic of China.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, People's Republic of China.
J Exp Clin Cancer Res. 2020 Aug 3;39(1):148. doi: 10.1186/s13046-020-01650-7.
Collagens are the most abundant proteins in extra cellular matrix and important components of tumor microenvironment. Recent studies have showed that aberrant expression of collagens can influence tumor cell behaviors. However, their roles in hepatocellular carcinoma (HCC) are poorly understood.
In this study, we screened all 44 collagen members in HCC using whole transcriptome sequencing data from the public datasets, and collagen type IV alpha1 chain (COL4A1) was identified as most significantly differential expressed gene. Expression of COL4A1 was detected in HCC samples by quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry (IHC). Finally, functions and potential mechanisms of COL4A1 were explored in HCC progression.
COL4A1 is the most significantly overexpressed collagen gene in HCC. Upregulation of COL4A1 facilitates the proliferation, migration and invasion of HCC cells through FAK-Src signaling. Expression of COL4A1 is upregulated by RUNX1 in HCC. HCC cells with high COL4A1 expression are sensitive to the treatment with FAK or Src inhibitor.
COL4A1 facilitates growth and metastasis in HCC via activation of FAK-Src signaling. High level of COL4A1 may be a potential biomarker for diagnosis and treatment with FAK or Src inhibitor for HCC.
胶原是细胞外基质中最丰富的蛋白质，也是肿瘤微环境的重要组成部分。最近的研究表明，胶原的异常表达可以影响肿瘤细胞的行为。然而，它们在肝细胞癌（HCC）中的作用还知之甚少。
在这项研究中，我们使用公共数据集的全转录组测序数据筛选了 HCC 中的所有 44 种胶原成员，发现胶原 IV 型α1 链（COL4A1）是差异表达最显著的基因。通过定量实时聚合酶链反应（qRT-PCR）、western blot 和免疫组织化学（IHC）检测 HCC 样本中 COL4A1 的表达。最后，探讨了 COL4A1 在 HCC 进展中的功能和潜在机制。
COL4A1 是 HCC 中表达最显著上调的胶原基因。COL4A1 的上调通过 FAK-Src 信号促进 HCC 细胞的增殖、迁移和侵袭。RUNX1 在 HCC 中上调 COL4A1 的表达。高 COL4A1 表达的 HCC 细胞对 FAK 或 Src 抑制剂的治疗敏感。
COL4A1 通过激活 FAK-Src 信号促进 HCC 的生长和转移。高水平的 COL4A1 可能是 HCC 诊断和 FAK 或 Src 抑制剂治疗的潜在标志物。
