Inhibition of the Interleukin-11-STAT3 Axis Attenuates Hypoxia-Induced Migration and Invasion in MDA-MB-231 Breast Cancer Cells.
10.4196/kjpp.2014.18.5.391
- Author:
Ji Hong LIM
1
Author Information
1. Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, Chungju 380-701, Korea. jhlim@kku.ac.kr
- Publication Type:Original Article
- Keywords:
Hypoxia;
Interleukin-11;
Invasion;
Migration;
STAT3
- MeSH:
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
- From:The Korean Journal of Physiology and Pharmacology
2014;18(5):391-396
- CountryRepublic of Korea
- Language:English
-
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.
