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.