Korean J Physiol Pharmacol.  2014 Oct;18(5):391-396. 10.4196/kjpp.2014.18.5.391.

Inhibition of the Interleukin-11-STAT3 Axis Attenuates Hypoxia-Induced Migration and Invasion in MDA-MB-231 Breast Cancer Cells

• Lim JH

• KMID: 2285537
• DOI: http://doi.org/10.4196/kjpp.2014.18.5.391

Abstract

Although interleukin-11 (IL-11) has been reported to be elevated in hypoxic tumors and has been associated with a poor prognosis in various cancers, little is known about its precise role in promoting metastasis in hypoxic tumors. In the present study, the molecular mechanism underlying the effects of IL-11 on MDA-MB-231 breast cancer cells migration and invasion in relation to metastasis under hypoxic conditions has been defined. Inhibition of IL-11 expression or function using small interfering RNA (siRNA) or a neutralizing antibody attenuated hypoxic MDA-MB-231 breast cancer cell migration and invasion through down-regulation of matrix metalloproteinases (MMPs) and activation of epithelial-to-mesenchymal transition (EMT) related gene expression. In addition, hypoxia-induced IL-11 increased STAT3 phosphorylation and STAT3 knockdown suppressed hypoxic MDA-MB-231 breast cancer cell invasion due to reduced MMP levels and reprogrammed EMT-related gene expression. These results suggest that one of the hypoxic metastasis pathways and the regulation of this pathway could be a potential target for novel cancer therapeutics.

Keyword

Hypoxia; Interleukin-11; Invasion; Migration; STAT3

MeSH Terms

Anoxia
Antibodies, Neutralizing
Axis, Cervical Vertebra*
Breast Neoplasms*
Cell Movement
Down-Regulation
Gene Expression
Interleukin-11
Matrix Metalloproteinases
Neoplasm Metastasis
Phosphorylation
Prognosis
RNA, Small Interfering
Antibodies, Neutralizing
Interleukin-11
Matrix Metalloproteinases
RNA, Small Interfering

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