Ovarian cancer is the 6th most common cancer among women in Hong Kong. The latest figures show that 651 cases of ovarian cancer were diagnosed in 2017, with 219 deaths in the same year. The causes and the molecular events that lead to the development of the disease remain largely unknown. Now a study by researchers at the LKS Faculty of Medicine, The University of Hong Kong (HKUMed) has revealed a signalling pathway triggered by a protein called p85β to promote the growth and progression of ovarian cancer cells. The findings are published in Nature Communications (link to the publication).
The research team discovered that p85β is often overexpressed in ovarian cancer cells, for example, through gene amplification. It is noteworthy that ovarian cancer patients with high levels of p85β showed worse survival outcomes, suggesting the clinical significance of p85β in the disease. In this study, it was found that p85β can enhance the growth and metastasis of ovarian cancer cells, providing an explanation of the high p85β levels in cancer cells and the associated worse prognosis. The team then took a closer look to understand how p85β expression favours tumorigenesis. Through proteomic profiling and subsequent validation, a cell surface signalling receptor protein called AXL was found to be activated by p85β, which protects AXL from degradation through selective autophagy which is a cellular process to target and degrade specific proteins. Being an initiator of cellular signalling, the activated AXL thereby causes a stimulation of downstream signalling pathway to promote cancer phenotypes.
“We know that p85β is an important component within the PI3K signalling network, but the role it plays in cancer was unclear.” Dr Lydia Cheung Wai-ting, who leads the research, says. "Thanks to the hard work of the team, we discover a previously unknown function of p85β in cancer and were able to dissect a new signalling mechanism that drives the development of ovarian cancer.”
This study identified p85β as a novel protein that contributes to ovarian tumorigenesis. Cancer cells rely on p85β for growth, targeting the signal of p85β has therefore the potential to beat cancer. The findings lay the foundation for the future development of new treatments by inhibiting cancer growth at its roots.
About the Research Team
The research was led by Dr Lydia Cheung Wai-ting, Assistant Professor of the School of Biomedical Sciences, HKUMed. Ms Ling Rao and Dr Victor Mak Chun-yin, School of Biomedical Sciences, HKUMed are co-first authors. Collaborators included Dr George Tipoe, Associate Professor of the School of Biomedical Sciences, Assistant Dean (Enrichment Year) and Director of Institute of Medical and Health Sciences Education, HKUMed; Professor Annie Cheung Nga-yin, Laurence L T Hou Professor in Anatomical Molecular Pathology at the Department of Pathology, HKUMed; Professor Gordon Mills at Knight Cancer Institute of Oregon Health & Science University, United States; Professor Yiling Lu at University of Texas MD Anderson Cancer Center, United States; and Dr Chao Gu at Fudan University, Shanghai.
The work was supported by Hong Kong Research Grants Council (#17111618).
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