Breast Cancer Metastasis Linked to Rho-Associated Kinase (ROCK) Activity

Metastasis of breast cancer to bone and other tissues was blocked by the inhibition of the enzyme Rho-associated kinase (ROCK) in a novel "human breast cancer metastasis to human bone" mouse model. ROCK signaling plays a fundamental role in regulating cell morphology, adhesion, and motility. Excessive expression of ROCK is related to tumor metastases and poor clinical outcome.

Investigators at Tufts University School of Medicine (Boston, MA, USA) studied breast cancer metastasis in a model system where it was possible to both amplify ROCK activity as well as to eliminate it.

They found that inserting high levels of ROCK into nonmetastatic cancer cells caused the cells to metastasize to several secondary sites, while cells with no added ROCK remained localized. In another study, an experimental drug (Y27632) or specific short hairpin RNA (shRNA) was used to inhibit ROCK activity in seven mice with metastatic tumors. Results published in the November 3, 2009, online edition of the journal Cancer Research, revealed a significant decrease in metastasis to bone in these animals as compared to six untreated mice.

"While the primary tumor causes significant illness and requires treatment, metastasis accounts for over 90% of breast cancer-related deaths. There are no treatments to eradicate metastasis. Establishing ROCK's role in the spread of breast cancer and identifying agents to inhibit ROCK brings us one step closer to an approach that might reduce metastasis in the future," said senior author Dr. Michael Rosenblatt, professor of physiology and medicine at Tufts University School of Medicine.

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