A5078684719- TGF-β signaling in diseases
- Ferroptosis and cancer prognosis
- MicroRNA in disease regulation
- Cellular Mechanics and Interactions
- Kruppel-like factors research
- Caveolin-1 and cellular processes
- Ovarian cancer diagnosis and treatment
- Cell Adhesion Molecules Research
- Angiogenesis and VEGF in Cancer
- Cancer-related molecular mechanisms research
- Cancer and biochemical research
- Elasticity and Material Modeling
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Peptidase Inhibition and Analysis
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Signaling Pathways in Disease
- Epigenetics and DNA Methylation
- Advanced Breast Cancer Therapies
- Mitochondrial Function and Pathology
- Fibroblast Growth Factor Research
- RNA Research and Splicing
- Hippo pathway signaling and YAP/TAZ
- Phagocytosis and Immune Regulation
University of Alabama at Birmingham
2020-2025
University of South Carolina
2015-2024
University of Alabama
2024
O'Neal Comprehensive Cancer Center
2024
Tel Aviv University
2021
Duke Medical Center
2006-2021
Duke University
2008-2021
University of Pittsburgh
2021
University of Arizona
2021
Quest International University Perak
2019
Cancer cells are defined by their ability to invade through the basement membrane, a critical step during metastasis. While increased secretion of proteases, which facilitates degradation and alterations in cytoskeletal architecture cancer have been previously studied, contribution mechanical properties invasion is unclear. Here, we applied magnetic tweezer system establish that stiffness patient tumor cell lines inversely correlates with migration three-dimensional membranes, correlation...
Loss of expression the TGF-beta superfamily coreceptor, type III receptor (TbetaRIII or betaglycan), occurs in a broad spectrum human cancers including breast, lung, ovarian, pancreatic, prostate, and renal cell cancer. TbetaRIII suppresses cancer progression vivo, at least part, by reducing motility. However, mechanism which regulates migration is unknown. Here, we demonstrate an unexpected signaling independent role for activating Cdc42, altering actin cytoskeleton directional persistence...
Abstract Unresectable hepatic metastases of colon cancer respond poorly to existing therapies and are a major cause lethality. In this study, we evaluated the therapeutic viability targeting mediator kinase CDK8, an early clinical stage drug target, as means suppress metastasis cancer. CDK8 was amplified or overexpressed in many cancers expression correlated with shorter patient survival. Knockdown inhibition had little effect on cell growth but suppressed metastatic mouse human cells liver....
Growth factors in tumor environments are regulators of cell survival and metastasis. Here, we reveal the dichotomy between TGF-β superfamily growth BMP TGF-β/activin their downstream SMAD effectors. Gene expression profiling uncovers SOX2 as a key contextual signaling node regulated an opposing manner by BMP2, -4, -9 activin A to impact anchorage-independent survival. We find that is repressed BMPs, leading reduction intraperitoneal burden improved tumor-bearing mice. Repression driven...
Recent studies implicate a role for cell mechanics in cancer progression. The epithelial-to-mesenchymal transition (EMT) regulates the detachment of cells from epithelium and facilitates their invasion into stromal tissue. Although classic EMT hallmarks include loss cell-cell adhesions, morphology changes, increased capacity, little is known about associated mechanical changes. Previously, force application on integrins has been shown to initiate cytoskeletal rearrangements that result...
Ovarian cancer remains the most lethal gynecologic malignancy, and is primarily diagnosed at late stage when considerable metastasis has occurred in peritoneal cavity. At abdominal cavity ascites accumulation provides a tumor-supporting medium which cells gain access to growth factors cytokines that promote survival metastasis. However, little known about redox status of ascites, or whether antioxidant enzymes are required support ovarian during transcoelomic this medium. Gene expression...
Acetylation of microtubules (MT) confers mechanical stability necessary for numerous functions including cell cycle and intracellular transport. Although αTAT1 is a major MT acetyltransferase, how this enzyme regulated remains much less clear. Here we report TGF-β-activated kinase 1 (TAK1) as key activator αTAT1. TAK1 directly interacts with phosphorylates at Ser237 to critically enhance its catalytic activity, mutating site alanine abrogates, whereas phosphomimetic induces hyperacetylation...
In budding yeast, the mitotic spindle is comprised of 32 kinetochore microtubules (kMTs) and ∼8 interpolar MTs (ipMTs). Upon anaphase onset, kMTs shorten to pole, whereas ipMTs increase in length. Overlapping are responsible for maintenance integrity during anaphase. To dissect requirements stability, we introduced a conditionally functional dicentric chromosome into yeast. When centromeres from same sister chromatid attach opposite poles, elongation delayed DNA breakage-fusion-bridge cycle...
Transforming growth factor-β (TGF-β) plays an important role in regulating hematopoiesis, inhibiting proliferation while stimulating differentiation when appropriate. We previously demonstrated that the type III TGF-β receptor (TβRIII, or betaglycan) serves as a novel suppressor of cancer progression epithelial tumors; however, its hematologic malignancies is unknown. Here we demonstrate TβRIII protein expression decreased lost majority human multiple myeloma specimens. Functionally,...
Background/Objective: Ovarian clear cell carcinomas (OCCCs) are a rare histological subtype of epithelial ovarian cancer characterized by resistance to platinum-based therapy. CDK8/19, component the regulatory CDK module associated with Mediator complex, has been implicated in transcriptional reprogramming and drug various solid tumors. Our study aimed investigate therapeutic potential CDK8/19 kinase inhibition using selective inhibitors SNX631 SNX631-6 OCCC treatment, both as monotherapy...
Growth factors and their receptors coordinate neuronal differentiation during development, yet roles in the pediatric tumor neuroblastoma remain unclear. Comparison of mRNA from benign neuroblastic tumors neuroblastomas revealed that expression type III TGF-β receptor (TGFBR3) decreases with advancing stage this loss correlates a poorer prognosis. Patients MYCN oncogene amplification low TGFBR3 were more likely to have an adverse outcome. In vitro, TβRIII was epigenetically suppressed by...
Abstract Inhibin is a heterodimeric TGFβ family ligand that expressed in many cancers and selective biomarker for ovarian cancers; however, its tumor-specific functions remain unknown. Here, we demonstrate the α subunit of inhibin (INHA), which critical functionality dimeric A/B, correlates with microvessel density human tissues predictive poor clinical outcomes multiple cancers. We inhibin-regulated angiogenesis necessary metastasis. Although had no direct impact on tumor cell signaling,...
Photophysics tunability through alteration of framework aperture (metal–organic (MOF) = variable; guest constant) was probed for the first time in comparison with previously explored concepts (MOF constant; variable). In particular, analysis confinement effect on a photophysical response integrated 5-(3-chlorobenzylidene)-2,3-dimethyl-3,5-dihydro-4H-imidazol-4-one (Cl-BI) chromophore allowed us to establish photophysics–aperture relationship. To shed light observed correlation, confined...
Abstract Defective angiogenesis underlies over 50 malignant, ischemic and inflammatory disorders yet long-term therapeutic applications inevitably fail, thus highlighting the need for greater understanding of vast crosstalk compensatory mechanisms. Based on proteomic profiling angiogenic endothelial components, here we report β IV -spectrin, a non-erythrocytic cytoskeletal protein, as critical regulator sprouting angiogenesis. Early loss endothelial-specific -spectrin promotes embryonic...