A5083222161- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- Protein Tyrosine Phosphatases
- RNA modifications and cancer
- Colorectal Cancer Treatments and Studies
- Metabolism, Diabetes, and Cancer
- Ion channel regulation and function
- Ubiquitin and proteasome pathways
- Hippo pathway signaling and YAP/TAZ
- Wnt/β-catenin signaling in development and cancer
- Neuropeptides and Animal Physiology
- Cancer-related Molecular Pathways
- Genetic factors in colorectal cancer
- Cancer-related gene regulation
- Cancer Cells and Metastasis
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Helicobacter pylori-related gastroenterology studies
- Epigenetics and DNA Methylation
- Pancreatic function and diabetes
- Cancer Treatment and Pharmacology
- Protein Kinase Regulation and GTPase Signaling
- Cardiac electrophysiology and arrhythmias
- Digestive system and related health
University of Kentucky
2016-2025
Markey Cancer Center
2016-2025
Northeast Normal University
2025
University of Notre Dame
2024
People's Liberation Army 401 Hospital
2024
Bridge University
2024
John Wiley & Sons (United States)
2019
University of Jordan
2019
Nielsen Engineering & Research (United States)
2019
University of California, San Diego
2001-2011
Abstract Activation of phosphoinositide 3-kinase (PI3K)/Akt signaling is associated with growth and progression colorectal cancer (CRC). We have previously shown that the mTOR kinase, a downstream effector PI3K/Akt signaling, regulates tumorigenesis CRC. However, contribution its interaction partners toward regulating CRC metastasis remains poorly understood. found increased expression mTOR, Raptor, Rictor mRNA was noted advanced stages CRC, suggesting may be metastasis. protein levels were...
Abstract We report here the identification of α1 Na/K-ATPase as a major regulator proto-oncogene Src kinase and role this regulation in control Warburg effect tumor growth. Specifically, we discovered Y260 Src-specific phosphorylation binding site that is required for Src-mediated signal transduction response to number stimuli including EGF. As such, it enables dynamic aerobic glycolysis. However, such appears be lost or attenuated human cancers expression was significantly decreased...
Obesity has been associated with increased incidence and mortality of a wide variety human cancers including colorectal cancer. However, the molecular mechanism by which adipocytes regulate metabolism colon cancer cells remains elusive. In this study, we showed that isolated from adipose tissues patients have an important role in modulating cellular to support tumor growth survival. Abundant were found close association invasive patients. Co-culture led transfer free fatty acids released...
Collagen prolyl 4-hydroxylase (P4H) expression and collagen hydroxylation in cancer cells are necessary for breast progression. Here, we show that P4H alpha 1 subunit (P4HA1) protein is induced triple-negative (TNBC) HER2 positive cancer. By modulating ketoglutarate (α-KG) succinate levels P4HA1 reduces proline on hypoxia-inducible factor (HIF) 1α, enhancing its stability cells. Activation of the P4HA/HIF-1 axis enhances cell stemness, accompanied by decreased oxidative phosphorylation...
Abstract Sterol regulatory element-binding proteins (SREBPs) belong to a family of transcription factors that regulate the expression genes required for synthesis fatty acids and cholesterol. Three SREBP isoforms, SREBP1a, SREBP1c, SREBP2, have been identified in mammalian cells. SREBP1a SREBP1c are derived from single gene through use alternative start sites. Here we investigated role SREBP-mediated lipogenesis regulating tumor growth initiation colon cancer. Knockdown either SREBP1 or...
The mammalian target of rapamycin (mTOR) kinase acts downstream phosphoinositide 3-kinase/Akt to regulate cellular growth, metabolism, and cytoskeleton. Because approximately 60% sporadic colorectal cancers (CRC) exhibit high levels activated Akt, we determined whether mTOR signaling pathway components are overexpressed in CRCs.HCT116, KM20, Caco-2, SW480 human CRC cells were used determine the effects pharmacologic (using rapamycin) or genetic RNAi) blockade on cell proliferation,...
// Yekaterina Y. Zaytseva 1 , Jennifer W. Harris 1, 2 Mihail I. Mitov Ji Tae Kim D. Allan Butterfield 3 Eun Lee 4 Heidi L. Weiss Tianyan Gao B. Mark Evers Markey Cancer Center, University of Kentucky, Lexington, USA Department Surgery, Chemistry, Pathology and Laboratory Medicine, Correspondence to: Evers, e-mail: mark.evers@uky.edu Keywords: FASN, colorectal cancer, energy homeostasis, metastasis, metabolic stress Received: March 11, 2015 Accepted: April 6,...
// Yekaterina Y. Zaytseva 1 , Piotr G. Rychahou 2, 3 Anh-Thu Le Timothy L. Scott 4 Robert M. Flight Ji Tae Kim 2 Jennifer Harris Jinpeng Liu Chi Wang Andrew J. Morris 5 Theru A. Sivakumaran Teresa Fan Hunter Moseley Tianyan Gao Eun Lee 6 Heidi Weiss S. Heuer 7 George Kemble and Mark Evers Department of Toxicology Cancer Biology, University Kentucky, Lexington, KY, USA Markey Center, Surgery, RC-SIRM, Cardiovascular Research, Pathology Laboratory Medicine, 3-V Biosciences, Menlo Park, CA,...
Activation of protein kinase A (PKA) through the β-adrenergic receptor pathway is crucial for positive regulation cardiac L-type currents; however it still unclear which phosphorylation events cause robust channel function. In order to study whether or not recently identified PKA sites on β2 subunit are functional significance, we coexpressed wild-type (WT) mutant subunits in tsA-201 cells together with an α1C subunit, α1CΔ1905, that lacked C-terminal 265 amino acids, including only site at...
The properties of cardiac L-type channels have been well characterized electrophysiologically, and many such studies demonstrated that the are regulated by a cAMP-dependent pathway. However, subunit composition native calcium has not completely defined. Furthermore, very important question exists regarding status C-terminal domain pore-forming α<sub>1</sub>subunit, as this potential to be target protein kinases but may truncated result post-translational processing. In present studies,...
Heat shock proteins play central roles in ensuring the correct folding and maturation of cellular proteins. Here we show that heat protein Hsp70 has a novel role prolonging lifetime activated kinase C. We identified screen for binding partners carboxyl terminus Co-immunoprecipitation experiments revealed specifically binds unphosphorylated turn motif (Thr641 C βII), one three priming sites phosphorylated during family members. The interaction with can be abolished vivo by co-expression...
Rationale: The recently discovered PHLPP-1 (PH domain leucine-rich repeat protein phosphatase-1) selectively dephosphorylates Akt at Ser473 and terminates signaling in cancer cells. regulatory role of the heart has not been considered. Objective: To test hypothesis that blockade/inhibition could constitute a novel way to enhance signals provide cardioprotection. Methods Results: is expressed neonatal rat ventricular myocytes (NRVMs) adult mouse (AMVMs). knockdown by small interfering RNA...
PHLPP1 belongs to a novel family of Ser/Thr protein phosphatases that serve as tumor suppressors by negatively regulating Akt signaling. Our recent studies have demonstrated loss PHLPP expression occurs at high frequency in colorectal cancer. In this study, we identified proteolytic target beta-TrCP-containing Skp-Cullin 1-F-box (SCF) complex (SCF(beta-TrCP)) E3 ubiquitin ligase phosphorylation-dependent manner. Overexpression wild-type but not DeltaF-box mutant beta-TrCP leads decreased and...
Upregulation of fatty acid synthase (FASN), a key enzyme de novo lipogenesis, is associated with metastasis in colorectal cancer (CRC). However, the mechanisms regulation are unknown. Since angiogenesis crucial for metastasis, we investigated role FASN neovascularization CRC. The effect on tumor vasculature was studied orthotopic CRCs, chick embryo chorioallantoic membrane (CAM) and Matrigel plug models using immunohistochemistry, immunofluorescent staining confocal microscopy. Cell...
PHLPP is a family of Ser/Thr protein phosphatases that contains PHLPP1 and PHLPP2 isoforms. We have shown previously functions as tumor suppressor by negatively regulating Akt signaling in cancer cells. Here we report the identification ribosomal S6 kinase 1 (S6K1) novel substrate PHLPP. Overexpression both isoforms resulted decrease S6K1 phosphorylation cells, this PHLPP-mediated dephosphorylation was independent its ability to dephosphorylate Akt. Conversely, increased cells depleted...