| الملخص: |
p47 is a cofactor protein of p97/valosin-containing protein (VCP), an Adenosine Triphosphatase (ATPase) that plays a role in regulating various cellular processes, such as autophagy, Golgi assembly, and protein degradation. It is one of forty cofactors associated with p97/VCP, and its interaction with p97/VCP is particularly important for Golgi assembly during mitosis. Previous research has suggested that p47 interacts with p97/VCPthrough its SHP domain, leading to increased SNAP REceptor (SNARE)-SNARE interactions between Golgi membranes. In a recent Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) knock-out (KO) screen conducted by Dr. Hao to identify metastatic tumor suppressor genes in human epidermal growth factor receptor 2 (HER2)+ breast cancer cells, p47 emerged as a top candidate. To delve deeper into the role of p47 in HER2+ breast cancer metastasis, this thesis aimed to explore its background and its impact on Golgi morphology (therefore potentially its functions) in HER2+ breast cancer cells.This research used two HER2+ cell lines, murine N418 and human HCC-1954 cells, and discovered that the presence or absence of p47 resulted in significant alterations in Golgi morphology in these cells. In the presence of p47, both cell lines exhibited a compact Golgi trans-face, specifically in non-dividing cells. Conversely, in the absence of p47, both cell lines displayed more puncta structures and increased spreading of the Golgi. Thesefindings were consistent with previous studies conducted on tumor protein p53 gene (p53) mutant MDA-MB-231 non-dividing cells. Mutations in p53, a tumor suppressor protein like p47, have been shown to cause greater Golgi fragmentation compared to cells with normal p53 levels. Overall, this thesis provides strong evidence for the critical role of p47 in maintaining Golgi morphology in HER2+ breast cancer cells. These findings have potential implications for understanding the mechanisms involved in breast cancer metastasis and identifying targets for therapeutic intervention. Additionally, the findings highlights the importance of Golgi morphology as a potential biomarker for cancer diagnosis and prognosis in the future. |
