The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
MTDH Activation by 8q22 Genomic Gain Promotes Chemoresistance and Metastasis of Poor-Prognosis Breast Cancer
Open accessAbstract
SUMMARY 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 the expression of 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. SIGNIFICANCE Genomic profiling of breast cancer has established several clinically applicable poor-prognosis gene signatures. However, the lack of overlap between independent signatures prevents the identification of functionally important genes in the signatures. Here we report an integrative strategy to identify recurrent genomic alterations that are both clinically relevant and functionally important for breast cancer progression. Successful application of this approach lead to the identification of MTDH at the recurrent 8q22 poor-prognosis genomic gain with important functions in both metastasis and chemoresistance. The dual-functionality of MTDH further provides an explanation for the long standing conceptual dilemma regarding the selection of metastasis genes in the primary tumor. Overall, our data illustrate the synergistic value of integrating bioinformatics with clinical and experimental metastasis research.
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MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
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A CXCL1 Paracrine Network Links Cancer Chemoresistance and Metastasis
Acharyya, S., Oskarsson, T., Vanharanta, S., Malladi, S., Kim, J., Morris, P. G., Manova-Todorova, K., Leversha, M., Hogg, N., Seshan, V. E., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.042 · Cited by 1,085
Metastatic heterogeneity of breast cancer: Molecular mechanism and potential therapeutic targets
Liang, Y., Zhang, H., Song, X., & Yang, Q. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.08.012 · Cited by 992
Self-citationMicroenvironmental regulation of therapeutic response in cancer
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Metadata
- Authors
- Hu, G., Chong, R. A., Yang, Q., Wei, Y., Blanco, M. A., Li, F., Reiss, M., Au, J. L.-S., Haffty, B. G., & Kang, Y.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 15
- Issue
- 1
- Pages
- 9-20
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2159796173
- Cited by
- 420
- References
- 39
- FWCI
- 10.30
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hu, G., Chong, R. A., Yang, Q., Wei, Y., Blanco, M. A., Li, F., Reiss, M., Au, J. L.-S., Haffty, B. G., & Kang, Y. (2009). MTDH Activation by 8q22 Genomic Gain Promotes Chemoresistance and Metastasis of Poor-Prognosis Breast Cancer. Cancer Cell. https://doi.org/10.1016/j.ccr.2008.11.013
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