Akt1 Protein Found to Trigger Metastasis and is Eyed as Chemotherapeutic Target

Cancer researchers have found that breast cancer cells require the protein Akt1 to develop and metastasize, which marks it as an attractive target for new chemotherapeutic drugs.

Akt1 is involved in cellular survival pathways through inhibition of apoptotic processes. It is also able to induce protein synthesis pathways, and is therefore a key signaling protein in the cellular pathways that lead to skeletal muscle hypertrophy and general tissue growth. Since it can block apoptosis, and thereby promote cell survival, Akt1 has been implicated as a major factor in many types of cancer.

Investigators at Thomas Jefferson University (Philadelphia, PA, USA) genetically engineered a line of mice to lack the gene for Akt1 synthesis. They then bred these mice to those from a different cell line that overexpressed the HER2-neu (ErbB2) oncogene, which leads to nearly 25% of breast cancers.

Results published in the April 25, 2007, online edition of the Proceedings of the [U.S.] National Academy of Sciences revealed that animals completely lacking Akt1 failed to produce any tumors. Those with one copy of the Akt1 gene developed some small, slowly developing tumors that failed to spread. Mice with two copies of the Akt1 gene developed aggressive tumors. Tumor cells from these animals secreted a factor--CXCL16-- that promoted breast cancer cell migration.

"These findings were exciting because they told us that Akt1 is a potentially useful target for ErbB2-positive breast cancer,” said senior author Dr. Richard Pestell, professor of cancer biology at Thomas Jefferson University. "Most interesting was that even if the mouse developed a tumor, it did not develop metastases. We proved that there was a requirement for Akt1 in metastasis, which makes Akt1 an exciting target for metastatic breast cancer. We knew that Akt1 could play a role in cell growth and size, but the idea that it could play a role in migration and metastasis was an unexpected new finding. We would like to find a way of blocking CXCL16 production and see if it is true in human breast cancers.”


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