Arginine deprivation inhibits pancreatic cancer cell migration, invasion and EMT via the down regulation of Snail, Slug, Twist, and MMP1/9

Huan Wang, Qing Fang Li, Hy Chow, Sc Choi, Yun Chung Leung (Corresponding Author)

Research output: Journal article publicationJournal articleAcademic researchpeer-review

7 Citations (Scopus)

Abstract

Arginine deprivation is currently being evaluated for its efficacy and safety in clinical trials aimed at combating tumors. However, the cellular signaling and molecular changes in response to such deprivation have not been systematically deciphered. Here, we evaluate the effect of arginine deprivation on human pancreatic cancer cells, with respect to their migratory and invasive potentials and their ability to undergo epithelial-mesenchymal transition (EMT). The transcription factors Snail, Slug, and Twist are regulators of EMT, as indicated by the suppression of E-cadherin and other epithelial markers and adhesion molecules. Our data indicated that arginine starvation inhibited the migration and impaired the adhesion and invasion of the pancreatic cancer cells, decreased Snail, Slug, and Twist expression, and increased E-cadherin expression without altering the expression of vimentin. It is well known that matrix metalloproteinases (MMPs) are important for the events that underlie tumor dissemination. Arginine starvation inhibited the expression of MMP-1 and MMP-9. Furthermore, the PI3K/Akt pathway was altered when the pancreatic cancer cells underwent arginine deprivation as exhibited by the decreased Akt phosphorylation. Thus, these data reveal that arginine deprivation has the potential to decrease the metastatic ability of pancreatic cancer cells.

Original languageEnglish
Pages (from-to)73-83
Number of pages11
JournalJournal of Physiology and Biochemistry
Volume76
Issue number1
DOIs
Publication statusPublished - 1 Feb 2020

Keywords

  • Arginine deprivation
  • EMT
  • invasion
  • migration
  • pancreatic cancer cells

ASJC Scopus subject areas

  • Biochemistry
  • Physiology

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