Study identifies Gα13 as key tumor suppressor in ER+ breast cancer

Searching for new ways to fight breast cancer, scientists from the Duke-NUS School of Medicine have uncovered the surprising role of a protein generally associated with cancer growth. They discovered that in estrogen receptor positive (ER+) breast cancer, this protein acts as a tumor suppressor. ER+ breast cancer accounts for about 80 percent of all breast cancer diagnoses, yet nearly 50 percent of women diagnosed with it experience a recurrence after initial treatment.

The unexpected finding contradicts long-held views that the protein, known as Gα13, acts as an accelerator of cancer cell growth, as seen with similar G-proteins. This latest discovery, published in the influential journal Breast cancer researchis the first study to identify Gα13 as a tumor suppressor in solid tumors. This could lead to new personalized approaches to breast cancer treatment that involve examining the levels of Gα13 and other proteins.

Our findings challenge the previous notion that Gα13 universally promotes cancer growth in different tumor types. Instead, we found evidence suggesting that Gα13 may help interrupt harmful pathways in estrogen receptor-positive breast cancer, potentially slowing or stopping the growth of cancer cells. This makes the discovery of a protective role for Gα13 all the more important, as it addresses a critical gap in understanding how different molecular pathways contribute to cancer progression.”

Dr. Lalitha Subramanyan, First Study Author and Postdoctoral Fellow, Department of Pharmacology and Cancer Biology, Duke University

The study findings have implications for a new direction in treatment strategies. Associate Professor Yap Yoon Sim, Department of Breast Medical Oncology & Gynecologic Oncology, National Cancer Center Singapore, who was not involved in the research, commented:

“Interestingly, the effects of the GNA13 protein differ in different types of cancer cells. These findings highlight the complexity of cancer biology and the need to understand the role of different molecules and pathways in different settings. We hope that this knowledge can facilitate development of new strategies for the treatment of breast cancer in the near future’.

Despite various advances in treatment, breast cancer remains the most diagnosed cancer worldwide and is the leading cause of cancer death in women, causing an estimated 685,000 deaths in 2020. In Singapore, breast cancer is the most common cancer in women . Almost one in three cancer diagnoses in women, according to the Singapore Cancer Society. This highlights the profound impact of the disease on women’s health, as well as the urgent need for more effective treatments.

Breast cancer is a complex disease, including several types that respond differently to treatments. The therapeutic approach varies depending on the molecular subtype.

Gα13 acts as a messenger inside cells, carrying signals from the cell surface to the inside of the cell, triggering a cascade of reactions that affect the cell’s behavior, including how it grows, divides, and responds to its environment. The study findings reveal a previously unknown relationship between Gα13 signaling and the hormone estrogen, an important determinant in breast cancer. Together, they control a prominent oncogene, MYC, and cancer cell growth.

Associate Professor Mei Wang from the Duke-NUS Cancer and Stem Cell Biology Program and co-corresponding author of the study, commented:

“In addition to expanding our understanding of Gα13 and related proteins in cancer formation, our findings also offer a new perspective for targeting recurrent ER+ cancers. While therapies for ER+ breast cancers primarily target ER signaling, nearly half of these patients develop resistance to such therapy Discovery of the control of estrogen signaling and MYC function offers new ways to treat resistant ER+ breast cancers.

During the study, a correlation was also observed between lower Gα13 levels and poorer patient survival outcomes in patients with ER+ breast cancer, further supporting the protective role of Gα13 against ER+ breast cancer.

The researchers plan to expand their study to investigate the role of Gα13 in other hormone-sensitive cancers and by applying these principles to other solid cancers.

Professor Patrick Tan, The Senior Vice-Chancellor for Research at Duke-NUS, commented:

“This study marks a definite and important advance, with potential implications for cancer treatment strategies. Understanding these molecular mechanisms paves the way for targeted drug development, which could enhance the effectiveness of breast cancer treatments and ultimately to improve survival rates and quality of life for those affected by this devastating disease.”