Regulation of signal transduction pathways by hypoxia in breast cancer subtypes

Liu, Q. (2023)

Doctoral Thesis

Breast cancer has a high mortality in women worldwide. Tumor cells experience hypoxia, which is accompanied by alterations in cell metabolism and can drive metastasis by triggering an epithelial–mesenchymal transition (EMT) in the tumor cells. Yes-associated protein (YAP) and a transcriptional co-activator with PDZ-binding (TAZ) are two transcriptional co-activators involved in growth, metabolism, and metastasis in cancer. Breast cancer can be divided into different subtypes. One criterium underlying such subtypes is based on the levels of Human Epidermal growth factor Receptor 2 (HER-2), Estrogen Receptor (ER) and Progesterone Receptor (PR). The subtypes include luminal-like (luminal A and luminal B), HER-2 enriched and basal-like (often “triple negative”). Triple negative breast cancer (TNBC) has a lower survival rate due to the lack of therapeutic targets. Fundamental research exploring the molecular mechanisms at work in cancer cells and their response to a hypoxic environment may contribute to insights for future clinical treatment. This thesis focused on profiling breast cancer cells belonging to distinct subtypes under acute and chronic hypoxia, investigating the crosstalk between hypoxia regulated pathways and YAP/TAZ signaling in luminal breast cancer versus TNBC cells, and identification of the potential targets of TAZ in breast cancer cells.

• Breast cancer
• YAP
• TAZ
• Chronic hypoxia
• Acute hypoxia
• Hypoxia
• Basal A
• TNBC
• Hippo signaling
• HIF pathway

• All authors: Liu, Q.
• Supervisor: Danen, E.H.J.
• Co-supervisor: Le Dévédec, S.E.
• Committee: Irth, H.; Bouwstra, J.A.; Water, B. van de; Bonnet, S.A.; Dijke, P. ten; Vooijs, M.A.G.G.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden Academic Centre for Drug Research (LACDR), Faculty of Science, Leiden University
• Date: 2023-02-09
• ISBN (print): 9789464588552