Naturally produced protein AKAP8 found to suppress spread of breast cancer

A protein naturally produced in the human body, known as AKAP8 (A-Kinase Anchor Protein) has been found to supress the metastasis (spread) of breast cancer. A groundbreaking study from researchers at Baylor College of Medicine in Houston, Texas found AKAP8 to be an important regulator in metastasis of tumors. High levels of AKAP8 also forecast a better survival rate for breast cancer patients.

Researchers at Baylor had previously been researching cellular mechanisms that could possibly regulate or inhibit breast cancer metastasis. One such process, called alternative splicing, was found to control tumor metastasis in a 2019 study. Alternative splicing is a natural cellular process in which a cell produces a large number of proteins from a small number of protein-encoding genes. (Imagine putting together several different outfits by combining a small set of clothes in different orders.) This helps the cell with anything from wound healing to embryonic development. Around 95 percent of all human genes are processed through alternative splicing, and it is crucial for the versatility of our genetic code. However, it was only recently that the role of alternative splicing in cancer has been looked into.

AKAP8 is a type of scaffolding protein, which help a cell hold its structure and transport molecules from place to place. In mouse cancer cell models, it was found that depletion of AKAP8 promoted breast cancer metastasis, while providing an external source of the protein inhibited metastasis. It was found that AKAP8 regulates the alternative splicing processes of other proteins, such as CD44 and CLSTN1S, the later of which is associated with preventing cells from metastasizing.

“We think that modulators of alternative splicing participate in a delicate balancing act of many different cellular proteins. Two types of modulators alternative splicing toward the production of proteins that help cells remain in a normal state. The other type tips the balance toward proteins that promote metastatic transformation. If the balance is disturbed, tumor progression can be promoted. By investigating how the balance is kept and the factors that disturb the balance, we hope to understand a new layer of regulation of tumor metastasis and gain insights that could lead to treatments for metastatic cancer, a deadly disease.

Dr. Chonghui Cheng, Author and Associate Professor at the Lester and Sue Smith Breast Center at Baylor College of Medicine

This potential form of protein-based cancer treatment is not the first of its kind. Another example is BXQ-350, which consists of a natural human protein (Saposin C) combined with nanobubbles of a fat molecule. BXQ-350 is able to find and kill cancerous cells without destroying healthy tissues. In addition, the chemical properties of the fat molecule allow it to pass through the blood brain barrier, making it particularly useful in treating brain cancers such as glioblastomas (malignant tumors affecting the brain and spine). While many synthetic procedures are showing promise in initial testing, continuation of research into the body’s natural defense mechanisms against cancer can prove extremely useful in our fight to develop treatments.

Original story and interview by Molly Chiu of Baylor College of Medicine.

References

1. Hu X, Harvey SE, Zheng R, Lyu J, Grzeskowiak CL, Powell E, Piwnica-Worms H, Scott KL, Cheng C. 2020. The RNA-binding protein AKAP8 suppresses tumor metastasis by antagonizing EMT-associated alternative splicing. Nature Communications.
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