Hepatocyte growth factor inhibits anoikis in head and neck carcinoma.

2003 MAR 4 - (NewsRx.com & NewsRx.net) -- According to recent research from the United States, "Anoikis, also called suspension-induced apoptosis, plays an important role in tumor development, progression, and metastasis.

"Recently we found that hepatocyte growth factor (HGF) inhibited anoikis of human head and neck squamous cell carcinoma (HNSCC) cells by activating the extracellular signal-regulated kinase (ERK)-signaling pathway. However, the antiapoptotic effectors that were regulated by the ERK-signaling pathway were unknown," wrote Q.H. Zeng and colleagues, University of Michigan, Department of Biology & Materials Science.

"Here we report that HGF-mediated inhibition of anoikis was dependent on activator protein-1 activity through the activation of the ERK-signaling pathway. Using a combination of microarray analysis and Northern blot analysis, we found that an antiapoptotic gene cyclooxygenase-2 (cox-2) was induced by HGF in an activator protein-1-dependent fashion.

"Inhibition of Cox-2 activity partially abolished HGF-mediated cell survival, and overexpression of Cox-2 in HNSCC cells provided resistance against anoikis. Moreover, HNSCC cells stably expressing Cox-2 had aggressive tumor growth in a nude mouse model compared with control cells," Zeng and coauthors stated.

The researchers concluded: "Taken together, our results demonstrate that Cox-2 plays an important role in HGF-mediated anoikis resistance. HGF may stimulate the progression and growth of HNSCC in vivo by induction of Cox-2."

Zeng and colleagues published their study in the Journal of Biological Chemistry (Hepatocyte growth factor inhibits anoikis by induction of activator protein 1-dependent cyclooxygenase-2 - Implication in head and neck squamous cell carcinoma progression. J Biol Chem, 2002;277(51):50137-50142).

For additional information, contact C.Y. Wang, University of Michigan, Department of Biology & Materials Science, Laboratory of Molecular Signaling & Apoptosis, 1011 N. University Avenue, Ann Arbor, MI 48109, USA.

To subscribe to the Journal of Biological Chemistry, contact the publisher: American Society of Biochemistry and Molecular Biology, Inc., 9650 Rockville Pike, Bethesda, MD 20814-3996, USA.

The information in this article comes under the major subject areas of Cell Biology and Oncology.

This article was prepared by Cancer Weekly editors from staff and other reports.