Baylor Breakthrough Gives Hope To Those Fighting Breast Cancer

Chris Fox
January 29, 2020 - 6:25 am
Baylor Scott and White Hospital

Alan Scaia

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WACO (1080 KRLD) - A protein naturally produced in the body has been found to suppress breast cancer metastasis in animal models of human tumors.

Researchers led by Baylor College of Medicine also found that high levels of this protein, AKAP8, predicts a better survival for breast cancer patients.

The findings, in the current edition of the journal Nature Communications, show that AKAP8 inhibits metastasis by interfering with the production of proteins that promote metastatic behavior in cells, and suggest strategies that may help treat metastatic cancer in the future.

“Our laboratory investigates cellular mechanisms that regulate breast cancer metastasis. In a previous study we provided the first evidence that alternative splicing, a cellular process that enables cells to switch between different forms of the same protein, can functionally control tumor metastasis,” said corresponding author Dr. Chonghui Cheng, associate professor at the Lester and Sue Smith Breast Center, of molecular and human genetics and of molecular and cellular biology at Baylor.

Alternative splicing is a natural cellular process that helps cells conduct many functions, such as wound healing and embryonic development. Through alternative splicing, cells can make a large number of proteins from a limited number of genes. It would be like putting together a number of different outfits by combining in different ways a limited number of pieces of clothing. In humans, around 95 percent of all genes are processed through alternative splicing. Just recently has this process also been shown to be involved in cancer.

In that pioneering study that brought alternative splicing to the field of cancer research, Cheng and her colleagues showed that of the two distinct forms of the protein CD44 that can be produced by alternative splicing, named CD44s and CD44v, only the former contributed to cancer cell survival. These findings have been confirmed by other reports about breast cancer and also other types of cancer.

In the current study, the researchers further investigated how alternative splicing contributes to cancer metastasis by looking for proteins that regulate alternative splicing events linked to metastasis.

AKAP8 helps keep cells in a non-metastatic state

Cheng and her colleagues screened cells looking for proteins functioning as alternative splicing modulators that prevented cells from becoming metastatic. They identified a set of proteins that were potentially key for tumor metastasis regulation and focused on AKAP8.

“We studied AKAP8 in metastatic breast cancer animal model systems of cancer cells from human patients,” Cheng said. “We found that depletion of the AKAP8 protein in patient cancer cells promoted breast cancer metastasis in these mouse models. Furthermore, providing an external source of AKAP8 inhibited metastasis.”

Taking it all together, the results support AKAP8 as an important regulator of alternative splicing events linked to tumor metastasis. It is not only able to predict metastatic breast cancer outcomes in patients, but also can inhibit metastatic breast cancer progression in animal models.