The metadherin gene (MTDH) plays a role in both cancer metastasis and resistance to chemotherapy, and can be a promising therapeutic target for high-risk breast cancers, according to a new study published in the Cancer Cell journal Tuesday.
"Most breast cancer patients resist currently available therapeutic regimens and succumb to recurrent tumors that spread to distant vital organs, such as lungs, bone, liver and brain," said senior study author Dr. Yibin Kang of Princeton University's Department of Molecular Biology.
Vasiliki Kostoula, a Greek breast cancer patient, smiles after a radiological medical examination in an Athens hospital October 29, 2008.(Xinhua/Reuters Photo) "Resistance to chemotherapy and metastasis remain major challenges to curative therapy," he said.
Previous research identified several clinically applicable genetic signatures associated with poor clinical outcomes of breast cancer. However, the signatures differed between independent studies, making it difficult to identify overlapping, functionally relevant genes that might be useful for understanding, and eventually preventing, breast cancer metastasis and chemoresistance.
To further unravel the complex genetic events involved in breast cancer, Dr. Kang and his colleagues developed a sophisticated computational algorithm designed to identify genomicchanges in an extensive collection of breast tumor samples.
The researchers discovered abnormally high copy numbers of chromosomal region 8q22 in more than 30 percent of breast cancers examined. Patients having this type of breast cancer often had a shorter survival time due to recurrent and metastatic cancers.
The researchers went on to find that among a handful of genes in the 8q22 region, MTDH was responsible for both increased metastasis and increased resistance to chemotherapeutics. MTDH protein increased metastasis of breast cancers to distant organs by enhancing the binding of cancer cells to blood vessels in these organs.
In addition, MTDH protein promoted cell survival, allowing cancer cells to become more resistant to a wide variety of chemotherapeutic agents that are currently used to treat breast cancer.
Further, when the researchers genetically altered the cancer cells to reduce expression of MTDH, the tumor cells became less capable of metastasis and more likely to be eliminated by chemotherapeutic agents.
"These findings establish MTDH as an important therapeutic target for simultaneously enhancing chemotherapy efficacy and reducing metastasis risk," said Dr. Kang. "Molecular targeting of MTDH may not only prevent the seeding of breast cancer cells to the lung and other vital organs but also sensitize tumor cells to chemotherapy, thereby stopping the deadly spread of breast cancer."
Source:Xinhua
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