Keratin 17 upregulation promotes cell metastasis and angiogenesis in colon adenocarcinoma

Bioengineered. 2021 Dec;12(2):12598-12611. doi: 10.1080/21655979.2021.2010393.

Abstract

Colon adenocarcinoma (COAD), having high malignancy and poor prognosis, is the main pathological type of colon cancer. Previous studies show that Keratin 17 (KRT17) plays an important role in the development of many malignant tumors. However, its role and the molecular mechanism underlying COAD remain unclear. Using TCGA and ONCOMINE databases, as well as immunohistochemistry, we found that the expression of KRT17 was higher in COAD tissues as compared to that in the adjacent normal tissues. Cell- and animal-based experiments showed that overexpression of KRT17 promoted the invasion and metastasis of colon cancer cells while knocking down KRT17 reversed these processes both in vitro and in vivo. In addition, we also showed that KRT17 promoted the formation of new blood vessels. Mechanistically, KRT17 could regulate the WNT/β-catenin signaling pathway, and APC may be involved in this process by interacting with KRT17. In summary, these findings suggested that high expression of KRT17 could promote cell metastasis and angiogenesis of colon cancer cells by regulating the WNT/β-catenin signaling pathway. Thus, KRT17 could be a potential therapeutic target for COAD treatment.

Keywords: Colon adenocarcinoma; KRT17; angiogenesis; metastasis; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics
  • Adenomatous Polyposis Coli Protein / metabolism
  • Animals
  • Cell Line, Tumor
  • Chickens
  • Colonic Neoplasms / blood supply*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Keratin-17 / genetics*
  • Keratin-17 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neovascularization, Pathologic / genetics*
  • Up-Regulation* / genetics
  • Wnt Signaling Pathway / genetics

Substances

  • Adenomatous Polyposis Coli Protein
  • Keratin-17

Grants and funding

This work was supported by the National Natural Science Foundation of China (82000497), Natural science foundation of Jiangsu Province (BK20200965), China Postdoctoral Science Foundation (2019M661909), and the Social Development Science and Technology Program of Nantong City (JC2019041).