A5048537006- Cancer-related Molecular Pathways
- RNA modifications and cancer
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Cancer Research and Treatments
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Pancreatic and Hepatic Oncology Research
- Cancer, Hypoxia, and Metabolism
- Virus-based gene therapy research
- Sarcoma Diagnosis and Treatment
- Cancer Cells and Metastasis
- interferon and immune responses
- Cell death mechanisms and regulation
- MicroRNA in disease regulation
- Cancer, Lipids, and Metabolism
- Protein Degradation and Inhibitors
- Ferroptosis and cancer prognosis
- Ubiquitin and proteasome pathways
- Cancer-related molecular mechanisms research
- Vascular Tumors and Angiosarcomas
- Cancer-related gene regulation
- Hedgehog Signaling Pathway Studies
- Bioinformatics and Genomic Networks
- Protease and Inhibitor Mechanisms
The University of Texas MD Anderson Cancer Center
2016-2025
Crown Bioscience (China)
2025
Guangzhou University of Chinese Medicine
2024
Jilin University
2024
The University of Texas Health Science Center at Houston
2022-2023
Pediatrics and Genetics
2013-2022
Tianjin Medical University Cancer Institute and Hospital
2018
Dalian Medical University
2016-2017
Cancer Genetics (United States)
2005-2007
Universidad de León
2007
The mitochondria-mediated caspase activation pathway is a major apoptotic characterized by mitochondrial outer membrane permeabilization (MOMP) and subsequent release of cytochrome c into the cytoplasm to activate caspases. MOMP regulated Bcl-2 family proteins. This plays important roles not only in normal development, maintenance tissue homeostasis regulation immune system, but also human diseases such as disorders, neurodegeneration cancer. In past decades molecular basis this regulatory...
Abstract 5‐Fluorouracil (5‐ FU ) is one of the most commonly used chemotherapeutic agents in colon cancer treatment, but has a narrow therapeutic index limited by its toxicity. Melatonin exerts antitumor activity various cancers, it never been combined with 5‐ as an anticolon treatment to improve effect . In this study, we assessed such combinational use and investigated whether melatonin could synergize We found that significantly enhanced ‐mediated inhibition cell proliferation, colony...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal and characterized by early metastasis. Oncogenic KRAS mutations prevail in 95% of PDAC tumors co-occur with genetic alterations the TP53 tumor suppressor nearly 70% patients. Most are missense that exhibit gain-of-function phenotypes include increased invasiveness metastasis, yet extent direct cooperation between effectors mutant p53 remains largely undefined. We show oncogenic activate CREB1 to allow physical...
Mdm2 and Mdm4 are homologous RING domain-containing proteins that negatively regulate the tumor suppressor p53 under physiological stress conditions. The domain of encodes an E3-ubiquitin ligase promotes degradation. In addition, interact through their respective domains. in vivo significance Mdm2-Mdm4 heterodimerization regulation function is unknown. this study, we generated conditional allele lacking to investigate its role regulation. Our results demonstrate homozygous deletion prenatal...
The transcription factor p53 is a tumor suppressor. As such, the P53 gene frequently altered in human cancers. However, over 80% of mutations found cancers are missense that lead to expression mutant proteins not only lack transcriptional activity but exhibit new functions as well. Recent studies show restoration leads regression mice carrying deletions. therapeutic efficacy restoring tumors containing has been evaluated. Here we demonstrate wild-type halted growth inheriting p53R172H...
The TP53 tumor suppressor gene is mutated early in most of the patients with triple-negative breast cancer (TNBC). frequent alterations are missense mutations that contribute to aggressiveness. Here, we used an autochthonous somatic TNBC mouse model, which mutant p53 can be toggled on and off genetically while leaving microenvironment intact wild-type for identify physiological dependencies p53. In TNBCs develop this deletion two different hotspot p53R172H p53R245W mutants triggers...
Abstract Restoration of the tumor suppressor function tumor-associated p53 mutants, including Y220C substitution, has posed a significant challenge for therapeutic discovery. Here, we describe rezatapopt (PC14586), part series compounds designed to reactivate mutant. These restore by correcting its conformation and enabling it bind DNA activate downstream target genes, thus inducing anti-proliferative changes in cells. Our findings are supported biochemical structural analysis, vitro vivo...
Loss of Mdm2 or Mdm4 leads to embryo lethal phenotypes that are p53-dependent. To determine whether and inhibit p53 function redundantly in a more restricted cell type, conditional alleles were crossed neuronal specific Cre transgene delete the CNS. Mice lacking CNS developed hydranencephaly at embryonic day 12.5 due apoptosis, whereas deletion showed proencephaly phenotype 17.5 because cycle arrest apoptosis. The both genes, strikingly, contributed an even earlier severe phenotype....
The function of the p53 tumor suppressor to inhibit proliferation or initiate apoptosis is often abrogated in cells.Mdm2 and its homolog, Mdm4, are critical inhibitors that overexpressed human tumors.In mice, loss Mdm2 Mdm4 leads embryonic lethal phenotypes completely rescued by concomitant p53.To examine role a temporal tissue-specific manner determine relationships these each other, we generated conditional alleles.We deleted cardiomyocytes, since important processes heart development.Mice...
Significance Mutations of p53 occur in approximately 50% human cancer. missense mutations exhibit gain-of-function activities. In this study, we discovered a previously unidentified mechanism mutant osteosarcoma and mammary tumors. Our data indicate that binds to E26 transformation-specific motifs the Pla2g16 phospholipase promoter induce its expression, which leads more aggressive metastatic phenotypes. Thus, study implicates regulation lipid metabolism cancer cells confer gain-of-function....
The p53–Mdm2 feedback loop is perceived to be critical for regulating stress-induced p53 activity and levels. However, this has never been tested in vivo. Using a genetically engineered mouse with mutated response elements the Mdm2 P2 promoter, we show that loop-deficient P2/P2 mice are viable aphenotypic age normally. degradation kinetics after DNA damage radiosensitive tissues remains similar wild-type controls. Nonetheless, elevated mice. Enhanced p53-dependent apoptosis sensitizes...
Abstract TP53 mutations are the most frequent genetic alterations in breast cancer and associated with more aggressive disease worse overall survival. We have created two conditional mutant Trp53 alleles mouse that allow expression of Trp53R172H or Trp53R245W missense single cells surrounded by a normal stroma immune system. Mice few epithelial develop cancers high similarity to human including triple negative. p53R245W tumors exhibit metastases lung liver. Development p53R172H some requires...
Abstract Ewing's sarcoma is characterized by the t(11;22)(q24:q12) reciprocal translocation. To study effects of fusion gene EWS-FLI1 on development and tumor formation, a transgenic mouse model was created. A strategy conditional expression used to limit potentially deleterious certain tissues. In absence Cre recombinase, not expressed in mice, they had normal phenotype. When crossed Prx1-Cre mouse, which expresses recombinase primitive mesenchymal cells embryonic limb bud, EF mice were...
High levels of the critical p53 inhibitor Mdm4 is common in tumors that retain a wild-type allele, suggesting overexpression an important mechanism for inactivation during tumorigenesis. To test this hypothesis vivo, we generated transgenic mice with widespread expression Mdm4. Two independent lines mice, Mdm4(Tg1) and Mdm4(Tg15), developed spontaneous tumors, most prevalent which were sarcomas. determine whether also cooperated heterozygosity to induce tumorigenesis, p53(+/-) mice. These...
TP53 is the most frequently mutated gene in human cancer. Many mutant p53 proteins exert oncogenic gain-of-function (GOF) properties that contribute to metastasis, but mechanisms mediating these functions remain poorly defined vivo. To elucidate how GOF drives we developed a traceable somatic osteosarcoma mouse model initiated with either single mutation (p53R172H) or loss osteoblasts. Our study confirmed mice osteosarcomas increased metastasis as compared -null mice. Comprehensive...
The purpose of the present study was to characterize prevalence, associated factors, and construct a nomogram for predicting bone metastasis (BM) with different histological types lung cancer.This descriptive that basing on invasive cancer patients diagnosed between 2010 2014 in Surveillance, Epidemiology, End Results program. A total 125,652 adult were retrieved. Logistic regression analysis conducted investigate homogeneous heterogeneous factors BM occurrence. Nomogram constructed predict...
Abstract The majority of TP53 missense mutations identified in cancer patients are the DNA-binding domain and characterized as either structural or contact mutations. These exhibit inhibitory effects on wild-type p53 activity. More importantly, these also demonstrate gain-of-function (GOF) activities by increased metastasis, poor prognosis, drug resistance. To better understand which mutations, Li–Fraumeni syndrome, contribute to tumorigenesis, we generated mice harboring a novel germline...
To understand cholesterol-mediated regulation of human fatty acid synthase promoter I, we tested various 5′-deletion constructs I-luciferase reporter gene in HepG2 cells. The that contained only the Sp-1-binding site (nucleotides −82 to −74) and two tandem sterol regulatory elements (SREs; nucleotides −63 −46) did not respond cholesterol. Only containing a nuclear factor-Y (NF-Y) sequence, CCAAT sequence −90 −86), an Sp-1 SREs responded NF-Y-binding site, therefore, is essential for...
Although several loci for familial dilated cardiomyopathy (DCM) have been mapped, the origin of a large percentage DCM remains unclear. Mdm2, p53-negative regulator, protects cardiomyocytes from ischemic and reperfusion-induced cell death. Mdm4, homolog inhibits p53 activity in numerous types. It is unknown whether Mdm4 plays role inhibition fully differentiated tissues such as adult this associated with DCM.The conditional knockout heart by use cardiomyocyte-specific Cre (alphaMyHC-Cre)...
Osteosarcoma is a highly aggressive bone disease with tendency to metastasize the lung. The 5-year survival of patients metastatic osteosarcoma only 20 %. Many studies have demonstrated SDF-1/CXCR4 and MMP9 play important roles in metastasis malignant tumors, including osteosarcoma. aim this study was investigate association CXCR4 expression clinicopathological features pulmonary Using tumor tissue microarrays, we analyzed among 34 primary osteosarcomas 62 without metastasis. A median time...