Silencing of Kangai 1 C-terminal interacting tetraspanin suppresses progression of cholangiocarcinoma

Exp Cell Res. 2018 Mar 1;364(1):59-67. doi: 10.1016/j.yexcr.2018.01.028. Epub 2018 Jan 31.


Cholangiocarcinoma (CC) is the second most common primary hepatic malignancy. CC treatment options are very limited especially for patients with distant metastasis. Kangai 1 C-terminal interacting tetraspanin (KITENIN) is highly expressed in numerous cancers, but the role of KITENIN in CC remains unknown. Here, we have investigated for the first time the function of KITENIN in human CC cell lines (TFK-1, SZ-1), tissues and a CC mouse model (Alb-Cre/LSL-KRASG12D/p53L/L). KITENIN was expressed in 92.2% of human CC tissues, in murine CC samples and also in human CC cell lines. Knockdown of KITENIN by small interfering RNA (siRNA) effectively reduced proliferation, migration, invasion and colony formation in both intra- and extra-hepatic CC cells. The expression of epithelial-mesenchymal transition (EMT) markers like N-cadherin, Vimentin, Snail and Slug were suppressed in KITENIN knockdown CC cells. Our results indicate that KITENIN is crucial for cholangiocarcinogenesis and it might become a potential therapeutic target for human CC treatment.

Keywords: Cholangiocarcinoma; EMT; KITENIN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / pathology
  • Bile Duct Neoplasms / prevention & control*
  • Carrier Proteins / antagonists & inhibitors*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Movement
  • Cell Proliferation*
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / pathology
  • Cholangiocarcinoma / prevention & control*
  • Female
  • Gene Silencing*
  • Humans
  • Male
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • RNA, Small Interfering / genetics*
  • Tumor Cells, Cultured


  • Carrier Proteins
  • Membrane Proteins
  • RNA, Small Interfering
  • VANGL1 protein, human
  • Vangl1 protein, mouse