The role of hepatocyte growth factor activator inhibitor (HAI)-1 and HAI-2 in endometrial cancer

Keiichiro Nakamura, Atsushi Hongo, Junichi Kodama, Yuji Hiramatsu

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


Hepatocyte growth factor activator inhibitors (HAI-1 and HAI-2) are Kunitz-type serine protease inhibitors that have a broad inhibitory spectrum against serine proteases. This is the first study to investigate the role of HAI-1 and HAI-2 in endometrial cancer. We investigated the biological functions of HAI-1 and HAI-2 using KLE and HEC-251 endometrial cancer cell lines, thus HAI-1 and HAI-2 were examined in uterine normal endometrium, endometrial hyperplasia and cancer specimens by immunohistochemistry. HAI-1 and HAI-2 showed potential inhibitory effects on cell proliferation, migration and cellular invasion by reduction of matriptase and hepsin expression. This in turn led to an increase in the levels of E-cadherin and Slug, and a reduction in the levels of Vimentin, SIP1, Snail and Twist, and hence ER and PR signal transduction in endometrial cancer cells. The levels of HAI-1 and HAI-2 expression were significantly decreased in endometrial cancer specimens relative to the corresponding normal endometrium specimens. Low HAI-1 and HAI-2 expression was a significant predictor for a poor prognosis compared with high HAI-1 and HAI-2 expression. These findings indicate that HAI-1 and HAI-2 could be considered as therapeutic targets and used as favorable prognosis markers for endometrial cancer.

Original languageEnglish
Pages (from-to)2613-2624
Number of pages12
JournalInternational Journal of Cancer
Issue number11
Publication statusPublished - Jun 1 2011


  • HAI-1
  • HAI-2
  • endometrial cancer
  • favorable prognosis marker
  • tumor suppressor gene

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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