Metastasis-promoting Mts1(S100A4) protein belongs to the S100 family of Ca(2+)-binding proteins. A mouse strain with a germ-line inactivation of the S100A4 gene was generated. The mice were viable and did not display developmental abnormalities in the postnatal period. However, an abnormal sex ratio was observed in the litters with the S100A4-/- genotype, raising the possibility of a certain level of embryonic lethality in this strain. In all, 10% of 10-14-month-old S100A4-null animals developed tumors. This is a characteristic feature of mouse strains with inactivated tumor suppressor genes. Spontaneous tumors of S100A4-/- mice were p53 positive. Recently, we have shown that S100A4 interacts with p53 tumor suppressor protein and induces apoptosis. We proposed that impairment of this interaction could affect the apoptosis-promoting function of p53 that is involved in its tumor suppressor activity. The frequency of apoptosis in the spleen of S100A4-/- animals after whole-body gamma-irradiation was reduced compared to the wild-type animals. The same was true for the transcriptional activation of the p53 target genes - waf/p21/cip1 and bax. Taken together, these observations indicate that spontaneous tumors in S100A4-/- mice are a result of functional destabilization of p53 tumor suppressor gene.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/sj.onc.1207420 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Recent Perspectives on Anticancer Potential of Coumarin Against Different Human Malignancies: An Updated Review.
Food Sci Nutr
January 2025
Agricultural Extension Directorate, MAAR Damascus Syria.
Coumarins, a group of naturally occurring compounds, have been reported to demonstrate anticancer potential. These substances, distinguished by their combined benzene and α-pyrone rings, have been demonstrated to impact multiple cellular mechanisms essential for the initiation and advancement of cancer. These agents work in different ways that prevent different tumor cells from growing, spreading, and increasing.
View Article and Find Full Text PDFHere, we have discussed the molecular mechanisms of p53-responsive microRNAs dysregulation in response to genotoxic stress in diffuse large B-cell lymphoma (DLBCL) patients. The role of micro ribonucleic acids (microRNAs) in p53-signaling cellular stress has been studied. MicroRNAs are the small non-coding RNAs, which regulate genes expression at post-transcriptional level.
View Article and Find Full Text PDFAtypical Small Cell Lung Cancer: A New Malignancy Characterized by Chromothripsis, Carcinoid Tumors, and Wild-type RB1 and TP53.
Cancer Discov
January 2025
Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas.
Small cell lung cancer (SCLC) and pulmonary carcinoid tumors are traditionally seen as unrelated, with SCLC linked to smoking and characterized by biallelic loss of RB1 and TP53 and rapid progression. Rekhtman and colleagues upend these assumptions by discovering an "atypical" SCLC that arises in nonsmokers with intact RB1 and TP53 loci, chromothripsis-induced oncogene amplifications on extrachromosomal DNA, and frequent synchronous carcinoid tumors. See related article by Rekhtman et al.
View Article and Find Full Text PDFTumor cell-derived N-acetyl-aspartyl-glutamate reshapes the tumor microenvironment to facilitate breast cancer metastasis.
Sci Bull (Beijing)
December 2024
Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences; State Key Laboratory of Genetic Engineering; Cancer Institutes; Department of Oncology; Key Laboratory of Breast Cancer in Shanghai; The Shanghai Key Laboratory of Medical Epigenetics; Shanghai Key Laboratory of Radiation Oncology; The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology; Shanghai Medical College; Fudan University, Shanghai 200032, China; Jinfeng Laboratory, Chongqing 401329, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing 211166, China. Electronic address:
Neurotransmitters are increasingly recognized to play important roles in limiting anti-tumor immunity. N-acetyl-aspartyl-glutamate (NAAG) has been extensively studied in neurological disorders; however, its potential role in restricting anti-tumor immunity has not been investigated. Here, we demonstrated that NAAG or its synthetase RimK-like family member B (RIMKLB) significantly disrupted anti-tumor immunity by rewiring the myeloid progenitor differentiation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), which in turn promoted breast cancer growth and metastasis.
View Article and Find Full Text PDFMAF1 inhibits hepatocarcinogenesis by fostering an immunostimulatory tumor microenvironment.
J Immunother Cancer
January 2025
State Key Laboratory of Oncology in South China, and Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
Background: The biological significance of MAF1, a tumor suppressor, in carcinogenesis and immune response of hepatocellular carcinoma (HCC) remains unreported. Understanding the underlying mechanisms by which MAF1 enhances anti-tumor immunity in HCC is crucial for developing novel immunotherapy strategies and enhancing clinical responses to treatment for patients with HCC.
Methods: Mice were subjected to hydrodynamic tail vein injections of transposon vectors to overexpress AKT/NRas, or c-Myc, with or without wild-type (WT) or mutant-activated (-4A) MAF1, or short-hairpin MAF1 (shMAF1).
Want 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!