348P - HGFK1 inhibits bone metastasis in breast cancer through the TAK1/p38 MAPK signaling pathway

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Basic Science
Breast Cancer, Metastatic
Presenter Yanzhi Bu
Authors Y. Bu
  • Lianshui People's Hospital, 223400 - Lianshui, Jiangsu/CN

Abstract

Background

Breast cancer metastasis to bone represents a devastating complication of advanced breast cancer, frequently resulting in significant increases in morbidity and mortality. An understanding of the mechanisms that govern breast cancer metastasis at the molecular level should lead to more effective therapies. Recently, the kringle 1 domain of human hepatocyte growth factor (HGFK1) was identified as a candidate metastasis suppressor gene.

Methods

Here, we investigated whether HGFK1 is a key regulator of breast cancer bone metastasis.

Results

Of the 193 human breast carcinoma tissue samples examined, HGFK1 expression was positive in 82 (42.4%). The positive expression of HGFK1 was significantly associated with a better prognostic value (P < 0.001) and inversely correlated with bone metastasis (P = 0.003). The efficacy of adeno-associated virus carrying HGFK1 (AAV-HGFK1) in osteolytic bone metastasis was then evaluated using an in vivo bone metastasis model. AAV-HGFK1 significantly inhibited osteolytic bone metastasis and prolonged the survival of mice in this model (P < 0.01). In vitro, HGFK1 expression resulted in significant anti-invasion effects, enhanced the phosphorylation of TAK1, p38 MAPK and MAPKAPK2, and decreased the expression of receptor activator of NF-?B (RANK), which was abrogated by the p38 MAPK inhibitor SB203580.

Conclusions

This study shows for the first time that HGFK1 significantly inhibits the metastasis of breast cancer to bone by activating the TAK1/p38 MAPK signaling pathway and inhibiting RANK expression. Thus, AAV-HGFK1 treatment represents a potential therapy for bone metastasis in breast cancer.

Disclosure

All authors have declared no conflicts of interest.