Aurora-A, also known as Aik, BTAK, or STK15, is a centrosomal serine/threonine protein kinase, which is proto-oncogenic and is overexpressed in a wide range of human cancers. Besides gene amplification and mRNA overexpression, proteolytic resistance mechanisms are thought to contribute to overexpression of Aurora-A. However, it is not yet clear how overexpressed Aurora-A affects the expression of transformed phenotype. Here, we found that nuclear accumulation of Aurora-A was critical for transformation activity. Cellular protein fractionation experiments and immunoblot analysis demonstrated a predominance of Aurora-A in the nuclear soluble fraction in head and neck cancer cells. Indirect immunofluorescence using confocal laser microscopy confirmed nuclear Aurora-A in head and neck cancer cells, while most oral keratinocytes exhibited only centrosomal localization. The expression of nuclear export signal-fused Aurora-A demonstrated that the oncogenic transformation activity was lost on disruption of the nuclear localization. Thus, the cytoplasmic localization of overexpressed Aurora-A previously demonstrated by immunohistochemical analysis is not likely to correspond to that in intact cancer cells. This study identifies an alternative mode of Aurora-A overexpression in cancer, through nuclear rather than cytoplasmic functions. We suggest that substrates of Aurora-A in the cell nuclear soluble fraction can represent a novel therapeutic target for cancer.
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http://dx.doi.org/10.1002/mc.20525 | DOI Listing |
Cancer Cell Int
December 2024
Department of Applied Chemistry, Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Puli, Taiwan.
Introduction: Chronic alcohol consumption and tobacco usage are major risk factors for esophageal squamous cell carcinoma (ESCC). Excessive tobacco and alcohol consumption lead to oxidative stress and the generation of reactive carbonyl species (RCS) which induce DNA damage and cell apoptosis. This phenomenon contributes to cell damage and carcinogenesis in various organs including ESCC.
View Article and Find Full Text PDFBMC Oral Health
December 2024
Institue of Public Health & Social Sciences(IPH&SS), Khyber Medical University(KMU), Peshawar, Pakistan.
Background: Chronic tobacco use, in any form, induces significant cellular alterations in the oral mucosa. This study investigates four distinct cytomorphological changes in oral mucosal cells among smokeless tobacco users, examining their association across different genders and age groups.
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Int J Biochem Cell Biol
December 2024
Institute of Biology and Medicine, College of Life Science and Health, Wuhan University of Science and Technology, Wuhan, Hubei 430081, China; College of Biomedicine and Health, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China. Electronic address:
Considering the high degree of malignancy, recurrence rate and poor prognosis, exploring promising targets is an imperious strategy for colorectal carcinoma therapy. Recent studies have indicated that GABPα plays a role in cancer aggressiveness, but its exact function and regulatory mechanisms in colorectal cancer progression remain unclear. This study aims to explore the biological role of GABPα and its upstream regulator, miR-378a-5p, in modulating cancer progression.
View Article and Find Full Text PDFCell Signal
December 2024
Department of Maxillofacial and Otorhinolaryngology Oncology and Department of Head and Neck Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Tianjin Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, China; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China. Electronic address:
Nerves are often overlooked as key components of the tumor microenvironment. However, the molecular mechanisms underlying the reciprocal interactions between tumors and nerves remain largely unknown. In this study, we analyzed data from The Cancer Genome Atlas (TCGA) and identified a significant association between DKK1 expression and poor prognosis, as well as a correlation between DKK1 expression and myeloid-derived suppressor cell (MDSC) infiltration in head and neck squamous cell carcinoma (HNSCC) and pancreatic ductal adenocarcinoma (PDAC), two cancer types characterized by pronounced tumor-nerve interactions.
View Article and Find Full Text PDFImmunology
December 2024
Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California, USA.
Autoreactive, aberrantly activated lymphocytes that target myelin antigens in the central nervous system (CNS) are primary drivers of the autoimmune disease multiple sclerosis (MS). Proliferating cells including activated lymphocytes require deoxyribonucleoside triphosphates (dNTPs) for DNA replication. dNTPs can be synthesised via the de novo pathway from precursors such as glucose and amino acids or the deoxyribonucleoside salvage pathway from extracellular deoxyribonucleosides.
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