MTDH activation by 8q22 genomic gain promotes chemoresistance and metastasis of poor-prognosis breast cancer (Cancer Cell, 2009, 15:9-20)

報告日期: 2009/03/13
報告時間: 15:10/16:00
報告學生: 林麗芳
講評老師: 張 玲
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980313-1%20.pdf

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

 

Hu G, Chong RA, Yang Q, Wei Y, Blanco MA, Li F, Reiss M, Au JL, Haffty BG, Kang Y.

Cancer Cell 15, 9-20, 2009

 

Speaker: 林麗芳

Commentator: 張玲老師

Time: 2009/03/13 15:10-16:00

Place: Room 602

 

Abstract:

Metastasis, the spread of cancer from primary tumors to distant vital organs, is accompanied by myriad of genetic and epigenetic alterations accumulated along the way. However, lack of effective tools to study this complex problem has hindered the development of accurate prognostic methods and effective treatments for metastatic cancer. Targeted therapy for metastatic diseases relies on the identification of functionally important metastasis genes from a large number of random genetic alterations. Previous studies reported that the application of genomic profiling methods to unravel the genetic mystery of cancer metastasis[1]. The challenge of distinguishing crucial drivers of metastasis from thousands of bystander alterations remains a major bottleneck in metastasis research. In this study, the authors used a computational algorithm to integrate and identify recurrent genomic alterations that are both clinically relevant and functional important for breast cancer progression. They applied analysis of CNAs by expression data (ACE) method to analyze three separate studies have previously identified poor-prognosis gene set [2-4], and found that 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. Moreover, functional characterization of MTDH revealed its dual role in promoting metastatic seeding and enhancing chemoresistance. Furthermore, their findings also indicated that ALDH3A1 and MET are the MTDH downstream genes that contribute to its role in chemoresistance. All together, this study illustrate the synergistic value of integrating bioinformatics with clinical and experimental metastasis research and establish MTDH as an important therapeutic target for simultaneously enhancing chemotherapy efficacy and reducing metastasis risk.

 

References

1.   Kang, Y., Functional genomic analysis of cancer metastasis: biologic insights and clinical implications. Expert Rev Mol Diagn, 2005. 5(3): p. 385-95.

2.   van 't Veer, L.J., et al., Gene expression profiling predicts clinical outcome of breast cancer. Nature, 2002. 415(6871): p. 530-6.

3.   van de Vijver, M.J., et al., A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med, 2002. 347(25): p. 1999-2009.

4.   Wang, Y., et al., Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet, 2005. 365(9460): p. 671-9.