MTDH Activation by 8q22 Genomic Gain Promotes Chemoresistance and Metastasis of Poor-Prognosis Breast Cancer

Guohong Hu, Robert A. Chong, Qifeng Yang, Yong Wei, Mario A. Blanco, Feng Li, Michael Reiss, Jessie L.S. Au, Bruce Haffty, Yibin Kang

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Abstract

Targeted therapy for metastatic diseases relies on the identification of functionally important metastasis genes from a large number of random genetic alterations. Here we use a computational algorithm to map minimal recurrent genomic alterations associated with poor-prognosis breast cancer. 8q22 genomic gain was identified by this approach and validated in an extensive collection of breast tumor samples. Regional gain of 8q22 elevates expression of the metastasis gene metadherin (MTDH), which is overexpressed in more than 40% of breast cancers and is associated with poor clinical outcomes. Functional characterization of MTDH revealed its dual role in promoting metastatic seeding and enhancing chemoresistance. These findings establish MTDH as an important therapeutic target for simultaneously enhancing chemotherapy efficacy and reducing metastasis risk.

Original languageEnglish (US)
Pages (from-to)9-20
Number of pages12
JournalCancer Cell
Volume15
Issue number1
DOIs
StatePublished - Jan 6 2009

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Hu, G., Chong, R. A., Yang, Q., Wei, Y., Blanco, M. A., Li, F., Reiss, M., Au, J. L. S., Haffty, B., & Kang, Y. (2009). MTDH Activation by 8q22 Genomic Gain Promotes Chemoresistance and Metastasis of Poor-Prognosis Breast Cancer. Cancer Cell, 15(1), 9-20. https://doi.org/10.1016/j.ccr.2008.11.013