Format

Send to

Choose Destination
See comment in PubMed Commons below
Oncotarget. 2014 Sep 15;5(17):7458-70.

High mobility group Box-1 inhibits cancer cell motility and metastasis by suppressing activation of transcription factor CREB and nWASP expression.

Author information

  • 1Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY. State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.+ Contributed equally to this work.
  • 2Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY. Contributed equally to this work.
  • 3Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY.
  • 4State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.
  • 5Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD, USA.

Abstract

The ability to metastasize is a hallmark of malignant tumors, and metastasis is the principal cause of death of cancer patients. The High Mobility Group Box-1 (HMGB1) is a multifunction protein that serves as both a chromatin protein and an extracellular signaling molecule. Our current study demonstrated a novel mechanism of HMGB1 in the regulation of cancer cell actin polymerization, cell skeleton formation, cancer cell motility and metastasis. We found that knockdown of HMGB1 in human lung cancer A549 cells significantly increased cell β-actin polymerization, cell skeleton formation, cancer cell migration and invasion in vitro, as well as metastasis in vivo. And this increase could be inhibited by treatment of HMGB1 knockdown cells with recombinant human HMGB1. Further studies discovered that HMGB1 suppressed phosphorylation, nuclear translocation, and activation of CREB, by inhibiting nuclear translocation of PKA catalytic subunit. This reduces nWASP mRNA transcription and expression, further impairing cancer cell motility. Our findings on the novel mechanism underlying the HMGB1 anti-metastatic effect on cancer provides significant insight into the understanding of the nature of HMGB1 in cancer invasion and metastasis, further serving as key information for utilization of HMGB1 and its regulated downstream components as new targets for cancer therapy.

PMID:
25277185
PMCID:
PMC4202136
DOI:
10.18632/oncotarget.2150
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Impact Journals, LLC Icon for PubMed Central
    Loading ...
    Support Center