Strong association of ARK5 with tumor invasion and metastasis

J Exp Clin Cancer Res. 2004 Jun;23(2):263-8.

Abstract

We recently identified a novel human AMPK family member, ARK5, and discovered that is a major factor in Akt-dependent cancer cell survival and migration activity through activation of MT1-MMPs in vitro. The mRNA expression of other AMPK family members and ARK5 was measured using RT-PCR in human colorectal carcinoma cell lines DLD-1, WiDr, HCT-15, SW620, LoVo, SW480, and mRNA expression of AMPK-alpha1, SNARK, MELK and ARK5, but not AMPK-alpha2, was detected in every line. Quantitative-PCR (Q-PCR) to estimate the amount of ARK5 mRNA expression in the cell lines showed that there is a variety of ARK5 expressions among the cell lines and high expression was observed in a cell line derived from the metastatic lesion, LoVo. To determine the effect of ARK5 overexpression on metastasis in vivo, we established human pancreas cancer cell line PANC-1 stably transfected with ARK5 full-length expression vector (P/ARK) and DLD-1 stably transfected with the same vector (D/ARK). Migration assay showed a remarkable increase in the activity both in P/ARK and D/ARK, and an in vivo metastasis assay showed a marked increase of P/ARK in liver metastasis. Based on these observations, it is suggested that ARK5 expression is involved in cancer invasion and metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • AMP-Activated Protein Kinases
  • Cell Line, Tumor
  • Cell Movement
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Enzyme Activation
  • Gene Expression*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary*
  • Multienzyme Complexes / genetics
  • Neoplasm Invasiveness / genetics
  • Pancreatic Neoplasms / genetics
  • Protein Kinases / genetics*
  • Protein Serine-Threonine Kinases / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection

Substances

  • Multienzyme Complexes
  • RNA, Messenger
  • Repressor Proteins
  • Protein Kinases
  • MELK protein, human
  • NUAK1 protein, human
  • NUAK2 protein, human
  • PRKAA2 protein, human
  • Protein Serine-Threonine Kinases
  • AMP-Activated Protein Kinase Kinases
  • AMP-Activated Protein Kinases
  • PRKAA1 protein, human