Infection with high-risk human papillomaviruses is causally linked to cervical carcinogenesis. However, most lesions caused by high-risk HPV infections do not progress to cancer. Host cell mutations contribute to malignant progression but the molecular nature of such mutations is unknown. Based on a previous study that reported an association between liver kinase B1 (LKB1) tumor suppressor loss and poor outcome in cervical cancer, we sought to determine the molecular basis for this observation. LKB1-negative cervical and lung cancer cells were reconstituted with wild type or kinase defective LKB1 mutants and we examined the importance of LKB1 catalytic activity in known LKB1-regulated processes including inhibition of cell proliferation and elevated resistance to energy stress. Our studies revealed marked differences in the biological activities of two kinase defective LKB1 mutants in the various cell lines. Thus, our results suggest that LKB1 may be a cell-type specific tumor suppressor.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3843939 | PMC |
| http://dx.doi.org/10.1016/j.virol.2013.07.009 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Long-term neuropsychologic outcome of pre-emptive mTOR inhibitor treatment in children with tuberous sclerosis complex (TSC) under 4Â months of age (PROTECT), a two-arm, randomized, observer-blind, controlled phase IIb national multicentre clinical trial: study protocol.
Orphanet J Rare Dis
January 2025
Division of Pediatric Epileptology, Department of Pediatrics I, Medical Faculty of Heidelberg, Heidelberg University, Heidelberg, Germany.
Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder affecting multiple organ systems, with a prevalence of 1:6,760-1:13,520 live births in Germany. On the molecular level, TSC is caused by heterozygous loss-of-function variants in either of the genes TSC1 or TSC2, encoding the Tuberin-Hamartin complex, which acts as a critical upstream suppressor of the mammalian target of rapamycin (mTOR), a key signaling pathway controlling cellular growth and metabolism. Despite the therapeutic success of mTOR inhibition in treating TSC-associated manifestations, studies with mTOR inhibitors in children with TSC above two years of age have failed to demonstrate beneficial effects on disease-related neuropsychological deficits.
View Article and Find Full Text PDFApplication of a high-throughput swarm-based deep neural network Algorithm reveals SPAG5 downregulation as a potential therapeutic target in adult AML.
Funct Integr Genomics
January 2025
Intelligent OMICS Limited, Nottingham, United Kingdom.
Gene‒gene interactions play pivotal roles in disease pathogenesis and are fundamental in the development of targeted therapeutics, particularly through the elucidation of oncogenic gene drivers in cancer. The systematic analysis of pathways and gene interactions is critical in the drug discovery process for various cancer subtypes. SPAG5, known for its role in spindle formation during cell division, has been identified as an oncogene in several cancers, although its specific impact on AML remains underexplored.
View Article and Find Full Text PDFDNA-damage orchestrates self-renewal and differentiation via reciprocal p53 family and Hippo/Wnt/TGF-β pathway activation in embryonic stem cells.
Cell Mol Life Sci
January 2025
Cam-Su Genomic Resource Center, Medical College of Soochow University, Suzhou, China.
The mechanism by which DNA-damage affects self-renewal and pluripotency remains unclear. DNA damage and repair mechanisms have been largely elucidated in mutated cancer cells or simple eukaryotes, making valid interpretations on early development difficult. Here we show the impact of ionizing irradiation on the maintenance and early differentiation of mouse embryonic stem cells (ESCs).
View Article and Find Full Text PDFTargeting mutant p53: Evaluation of novel anti-p53 monoclonal antibodies as diagnostic tools.
Sci Rep
January 2025
Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
About 50% of all cancers carry a mutation in p53 that impairs its tumor suppressor function. The p53 missense mutation p53 (p53 in mice) is a hotspot mutation in various cancer types. Therefore, monoclonal antibodies selectively targeting clinically relevant mutations like p53 could prove immensely value.
View Article and Find Full Text PDFBioinformatics approaches to multi-omics analysis of the potential of CDKN2A as a biomarker and therapeutic target for uterine corpus endometrial carcinoma.
Sci Rep
January 2025
Biochemistry and Molecular Biology, College of Basic Medical Science, Chongqing Medical University, Chongqing, 400000, China.
Uterine corpus endometrial carcinoma (UCEC) is a significant cause of cancer-related mortality among women worldwide. Prior research has demonstrated an association between cyclin-dependent kinase inhibitor 2Â A (CDKN2A) and various tumors. As a member of the INK4 family, CDKN2A is involved in cell cycle regulation by controlling CDKs.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!