127P - Synergistic role of HIF-1α and Nav1.5 in potentiating breast cancer metastasis

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Breast Cancer, Metastatic
Translational Research
Presenter Hemaniswarri Dewi Dewadas
Citation Annals of Oncology (2016) 27 (suppl_9): ix35-ix41. 10.1093/annonc/mdw577
Authors H.D. Dewadas1, N.S. Kamarulzaman1, N.S. Yaacob2, N.F. Mokhtar1
  • 1Institute For Research In Molecular Medicine (informm), Universiti Sains Malaysia (Health Campus), 16150 - Kubang Kerian/MY
  • 2Department Of Chemical Pathology, School Of Medical Sciences, Universiti Sains Malaysia (Health Campus), 16150 - Kubang Kerian/MY

Abstract

Background

Hypoxia, a condition of low oxygen concentration especially in locally advanced solid tumors has emerged as a pivotal factor in tumor prognostic since it can initiate tumor progression and resistance to therapy. Under this condition, transcription factor HIF-1α is the major regulator that induces activation or repression of particular homeostatic regulatory genes leading to cancer cell survival and metastasis. Additionally, ion channels such as voltage-gated sodium channels (VGSCs), have been reported to be elevated in various metastatic cancer cells in the past two decades. Several recent studies captured VGSCs in having a mechanistic role in promoting invasion and migration. Specifically in aggressive breast cancer cells, an isoform of VGSCs, Nav1.5 exhibited an increased in expression. Since both HIF-1α and Nav1.5 are highly expressed in aggressive breast cancer cells, this study is designed to investigate the synergic contribution of HIF-1α and Nav1.5 which may provide a better strategy-plan to combat metastatic disease.

Methods

Herein, HIF-1α was stabilized using cobalt chloride, CoCl2 (hypoxia mimicking agent) in the less aggressive breast cancer, MCF-7 cells which lack of HIF-1α and Nav1.5. mRNA of Nav1.5 and CA9 (a common target gene of HIF-1α) was analyzed by relative real-time PCR. Nuclear protein for HIF-1α was measured using Western blotting. Growth, lateral motility and transwell migration assays were conducted to investigate metastatic properties of the cells.

Results

CoCl2 successfully increased HIF-1α nuclear protein and mRNA expression of CA9. This was followed by increased Nav1.5 mRNA expression. Although CoCl2 did not alter growth of MCF-7 cells, motility and migration were enhanced.

Conclusions

In conclusion, increased mRNA of HIF-1α leads to upregulation of Nav1.5 expression. In combination, both molecules promote breast cancer cell aggressiveness though possible interaction between the two needs further studies.

Clinical trial indentification

Legal entity responsible for the study

Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia

Funding

Universiti Sains Malaysia Research University Grant, (1001/CIPPM/813060)

Disclosure

All authors have declared no conflicts of interest.