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Project

Loss of phosphoglycerate dehydrogenase (PHGDH) promotes metastatization in triple-negative breast cancer

According to World Health Organization, breast cancer is the most frequent cancer among women, with 2.1 million cases diagnosed every year. As a result, breast cancer is the second leading causes of cancer-related death among women. Nonetheless, successfully treating the more aggressive breast cancer subtypes, such as triplenegative breast cancer (TNBC), poses a great challenge, mainly for the lack of effective therapeutic options to target metastasis. This is a direct consequence of our limited knowledge of the molecular events that confer metastatic ability to breast cancer cells. TNBC is defined by the genetic amplification of the metabolic enzyme phosphoglycerate dehydrogenase (PHGDH). PHGDH plays a key role in TNBC growth at the primary site, however its role in metastasis formation is unknown. I have discovered that PHGDH is surprisingly lost in the transition from primary tumor to metastasis, and that such event increases the aggressiveness of TNBC. Based on this exciting discovery, I will investigate the molecular mechanisms and dynamics of PHGDH loss in breast cancer metastasis and I will define the biological advantage that PHGDH loss grants to metastatic TNBC, ultimately explaining how it drives metastasis formation. The information I will obtain will contribute to fill the gap in our understanding of how TNBC metastatizes. On the long term perspective, this will lead to novel effective therapeutic options against TNBC, which are an unmet need in the clinics.
 

Date:1 Oct 2019 →  30 Sep 2023
Keywords:Triple-negative breast cancer, Gene amplification, Cancer metabolism, Moonlight metabolic enzyme function
Disciplines:Molecular and cell biology not elsewhere classified, Genetics, Regulation of metabolism, Medical metabolomics