The unexpected finding that a cellular protein called Gα13 might actually serve to protect against the common relapsing type of breast cancer, rather than encouraging its growth, opens up possibilities for more effective and innovative treatment options.
Researchers at Duke-NUS Medical School have uncovered a surprising function of a protein that has typically been linked to cancer growth. In the case of oestrogen receptor-positive (ER+) breast cancer, which accounts for about 80% of all breast cancer diagnoses, this protein may actually act as a tumor suppressor. Approximately 50% of women diagnosed with ER+ breast cancer experience a relapse after receiving initial treatment.
This groundbreaking discovery challenges existing beliefs that Gα13 promotes cancer cell proliferation, as is the case with similar G-proteins. The findings, published in the prominent journal Breast Cancer Research, are the first to recognize Gα13 as a tumor suppressor in solid tumors. This could pave the way for personalized treatment strategies that examine levels of Gα13 alongside other proteins in patients.
Dr. Lalitha Subramanyan, a PhD graduate from Duke-NUS (Class of 2024) and currently a postdoctoral fellow at Duke University’s Department of Pharmacology and Cancer Biology, who is the lead author of the study, stated:
“Our research contradicts the previously accepted idea that Gα13 universally accelerates cancer growth across various tumor types. Instead, we found indications that Gα13 may disrupt harmful pathways in oestrogen receptor-positive breast cancer, potentially slowing or halting cancer cell growth. This protective role of Gα13 is critically important, as it enhances our understanding of the different molecular pathways involved in cancer progression.”
The implications of this study may shift the focus of treatment strategies. Associate Professor Yap Yoon Sim from the Department of Breast & Gynaecological Medical Oncology at the National Cancer Centre Singapore, who was not part of the research, remarked:
“The fact that the GNA13 protein has varying effects in different breast cancer cell types is intriguing. These results underscore the complex nature of cancer biology and illustrate the necessity of grasping the roles of different molecules and pathways in various contexts. It is hoped that this information could lead to the creation of novel breast cancer treatment strategies in the near future.”
Breast cancer persists as the most diagnosed cancer globally and remains a leading cause of cancer-related deaths among women, resulting in around 685,000 fatalities in 2020. In Singapore, breast cancer is the most frequently diagnosed cancer in women, making up nearly one in three cancer diagnoses. This emphasizes the significant impact of the disease on women’s health and underscores the urgent need for more effective treatment solutions.
Breast cancer is a multifaceted disease, comprising various types that respond differently to treatments. Treatment approaches are tailored based on the distinct molecular subtype.
Gα13 serves as a key messenger within cells, conveying signals from the cell surface to its interior, triggering a series of reactions that affect how the cell behaves, including its growth, division, and response to the environment. The study has unveiled a previously unrecognized link between Gα13 signaling and the hormone oestrogen, which plays a crucial role in breast cancer. Together, they regulate a significant oncogene called MYC, which affects cancer cell growth.
Associate Professor Mei Wang from Duke-NUS’ Cancer and Stem Cell Biology Programme and co-corresponding author of the study noted:
“In addition to broadening our grasp of Gα13 and related proteins in cancer development, our findings also provide a new viewpoint on addressing recurrent ER+ cancers. Current treatments for ER+ breast cancers primarily target ER signaling, yet nearly half of these patients develop resistance over time. The revelation that Gα13 influences oestrogen signaling and MYC function offers new pathways to tackle resistant ER+ breast cancers.”
The research indicated a correlation between lower levels of Gα13 and worse survival rates in patients with ER+ breast cancer, reinforcing its potential protective role.
The team aims to expand their research to investigate the role of Gα13 in other hormone-sensitive malignancies and apply this understanding to other types of solid tumors.
Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, expressed:
“This study represents a significant and clear advancement that could influence cancer treatment strategies. Gaining insight into these molecular mechanisms lays the groundwork for the development of targeted therapies, which could enhance the effectiveness of breast cancer treatments and ultimately improve survival rates and the quality of life for those affected by this devastating illness.”
Duke-NUS is a leading institution in biomedical research, dedicated to enhancing lives by merging foundational scientific research with practical knowledge to deepen the understanding of prevalent diseases and to forge new treatment approaches.
