Unraveling multifaceted roles of Grainyhead-like transcription factor-2 in breast cancer

Coban, B. (2024)

Doctoral Thesis

Breast cancer is the most common cancer in women worldwide. Metastasis, the process by which cancer cells spread to other parts of the body, makes treatments less effective. It is important to unravel the mechanism of metastasis. The epithelial-mesenchymal transition (EMT) is one such mechanism involved in cancer progression and metastasis. EMT is regulated by a network of transcription factors including Grainyhead-like 2 (GRHL2). GRHL2 is an important transcription factor for cell epithelial identity. GRHL2 has been described as capable of stimulating tumor growth but at the same time suppressing EMT and therefore could inhibit metastasis. This dissertation focuses on GRHL2 and the genes controlled by this transcription factor. I investigated the functions of GRHL2 in different subtypes of breast cancer by turning off or on the GRHL2 gene. I also analyzed the changes in EMT caused by the manipulations of GRHL2 in different subtypes of breast cancer. The results show that GRHL2 can play different, and subtype-specific roles. Although this is basic research, it provides new insights that may lead to targeted treatments. Among other things, my research shows how GRHL2 regulates the interaction of tumors with the immune system and how it affects metastasis in breast cancer. This suggests that it deserves further investigation as a potential factor in the development of therapies.

• Breast cancer
• GRHL2
• Metastasis
• Immunology
• Cancer cell signaling

• All authors: Coban, B.
• Supervisor: Danen, E.H.J.
• Co-supervisor: Neubert, E.
• Committee: Irth, H.; Lange, E.C.M.de; Water, B. van de; Dijke, P. ten; Pluijm, G. van der
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden Academic Centre for Drug Research (LACDR), Faculty of Science, Leiden University
• Date: 2024-11-05
• ISBN (print): 9789464736113