Breast cancer is the most commonly diagnosed cancer and a leading cause of cancer death in women. Breast cancer could be divided into four subtypes: Luminal A, Luminal B, HER2, and Triple Negative Breast Cancer (TNBC). TNBC, accounts for around 15% of all breast cancer cases, is an aggressive and heterogeneous disease with poor prognosis and the shortest survival rate because of no targeted therapies.
Cancer stem cells, also known as tumor initiating cells, are a small cell population with unique characteristic, including self-renewal, and the ability to generate heterogenic lineage of cancer cells. The conventional cancer treatments fail to eliminate the cancer stem cells due to chemoresistance and recurrence. However, TNBC is enriched of cancer stem cells. Therefore, it is urgent to develop more effective therapeutics to target cancer stem cells for triple negative breast cancer treatment.
Dr. Ceshi CHEN Lab from Kunming Institute of Zoology found that metformin, a first-line drug for diabetes, significantly decreases the percentage of cancer stem cells in TNBC through testing the population of Aldehyde dehydrogenase (ALDH) positive cells and their mammosphere formation ability. They also revealed that metformin functions through the PKA - GSK3β - KLF5 pathway, which provided a new mechanism for regulation of KLF5. Additionally, the study indicated that PKA and KLF5 are potential therapeutic targets for TNBC treatment and supported the idea that metformin is a promising agent for the treatment of TNBC.
This study was supported by the National Nature Science Foundation of China (81325016 and U1602221 to CC, 81672639 to ZZ,U1502222, 81322038 and 81272930 to RL), the Yunnan Applied Basic Research Key Projects (2015FA027 to RL), the West Light Foundation of the Chinese Academy of Sciences(to RL) and the Youth Innovation Promotion Association and the Chinese Academy of Sciences (to RL).
This work was published online in Cell Discovery on April 18, 2017. Link to the article: https://www.nature.com/articles/celldisc201710
The working model.
(By Lin-Xi He)
Contact: Ceshi CHEN