Full Text Journal Articles by
Author Noel A Warfel

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PIM kinases alter mitochondrial dynamics and chemosensitivity in lung cancer.

Shailender S Chauhan, Rachel K Toth, Corbin C Jensen, Andrea L Casillas, David F Kashatus, Noel A Warfel,

Resistance to chemotherapy represents a major obstacle to the successful treatment of non-small-cell lung cancer (NSCLC). The goal of this study was to determine how PIM kinases impact mitochondrial dynamics, ROS production, and response to chemotherapy in lung cancer. Live-cell imaging and microscopy were used to determine the effect of ... Read more >>

Oncogene (Oncogene)
[2020, 39(12):2597-2611]

Cited: 1 time

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Hypoxia-induced PIM kinase and laminin-activated integrin α6 mediate resistance to PI3K inhibitors in bone-metastatic CRPC.

Rachel K Toth, Jack D Tran, Michelle T Muldong, Eric A Nollet, Veronique V Schulz, Corbin C Jensen, Lori A Hazlehurst, Eva Corey, Donald Durden, Christina Jamieson, Cindy K Miranti, Noel A Warfel,

Bone-metastatic castration-resistant prostate cancer (CRPC) is lethal due to inherent resistance to androgen deprivation therapy, chemotherapy, and targeted therapies. Despite the fact that a majority of CRPC patients (approximately 70%) harbor a constitutively active PI3K survival pathway, targeting the PI3K/mTOR pathway has failed to increase overall survival in clinical trials. ... Read more >>

Am J Clin Exp Urol (American journal of clinical and experimental urology)
[2019, 7(4):297-312]

Cited: 0 times

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Gene Editing of α6 Integrin Inhibits Muscle Invasive Networks and Increases Cell-Cell Biophysical Properties in Prostate Cancer.

Cynthia S Rubenstein, Jaime M C Gard, Mengdie Wang, Julie E McGrath, Nadia Ingabire, James P Hinton, Kendra D Marr, Skyler J Simpson, Raymond B Nagle, Cindy K Miranti, Noel A Warfel, Joe G N Garcia, Hina Arif-Tiwari, Anne E Cress,

Human prostate cancer confined to the gland is indolent (low-risk), but tumors outside the capsule are aggressive (high-risk). Extracapsular extension requires invasion within and through a smooth muscle-structured environment. Because integrins respond to biomechanical cues, we used a gene editing approach to determine if a specific region of laminin-binding α6β1 ... Read more >>

Cancer Res. (Cancer research)
[2019, 79(18):4703-4714]

Cited: 0 times

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The Tumor Microenvironments of Lethal Prostate Cancer.

William L Harryman, Noel A Warfel, Raymond B Nagle, Anne E Cress,

Localized prostate cancer (confined to the gland) generally is considered curable, with nearly a 100% 5-year-survival rate. When the tumor escapes the prostate capsule, leading to metastasis, there is a poorer prognosis and higher mortality rate, with 5-year survival dropping to less than 30%. A major research question has been ... Read more >>

Adv. Exp. Med. Biol. (Advances in experimental medicine and biology)
[2019, 1210:149-170]

Cited: 0 times

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Mechanisms Behind Resistance to PI3K Inhibitor Treatment Induced by the PIM Kinase.

Jin H Song, Neha Singh, Libia A Luevano, Sathish K R Padi, Koichi Okumura, Virginie Olive, Stephen M Black, Noel A Warfel, David W Goodrich, Andrew S Kraft,

Cancer resistance to PI3K inhibitor therapy can be in part mediated by increases in the PIM1 kinase. However, the exact mechanism by which PIM kinase promotes tumor cell resistance is unknown. Our study unveils the pivotal control of redox signaling by PIM kinases as a driver of this resistance mechanism. ... Read more >>

Mol. Cancer Ther. (Molecular cancer therapeutics)
[2018, 17(12):2710-2721]

Cited: 6 times

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Targeting PIM kinases to oppose hypoxia-mediated therapeutic resistance.

Shailender S Chauhan, Noel A Warfel,

Oncoscience (Oncoscience)
[2018, 5(9-10):254-255]

Cited: 0 times

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Hypoxia-Inducible PIM Kinase Expression Promotes Resistance to Antiangiogenic Agents.

Andrea L Casillas, Rachel K Toth, Alva G Sainz, Neha Singh, Ankit A Desai, Andrew S Kraft, Noel A Warfel,

Purpose: Patients develop resistance to antiangiogenic drugs, secondary to changes in the tumor microenvironment, including hypoxia. PIM kinases are prosurvival kinases and their expression increases in hypoxia. The goal of this study was to determine whether targeting hypoxia-induced PIM kinase expression is effective in combination with VEGF-targeting agents. The rationale ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2018, 24(1):169-180]

Cited: 8 times

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Targeting CDK4/6 to oppose hypoxia-mediated therapeutic resistance.

Noel A Warfel,

Cell Cycle (Cell cycle (Georgetown, Tex.))
[2017, 16(13):1241-1242]

Cited: 0 times

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Strange Bedfellows: Nuclear Factor, Erythroid 2-Like 2 (Nrf2) and Hypoxia-Inducible Factor 1 (HIF-1) in Tumor Hypoxia.

Rachel K Toth, Noel A Warfel,

The importance of the tumor microenvironment for cancer progression and therapeutic resistance is an emerging focus of cancer biology. Hypoxia, or low oxygen, is a hallmark of solid tumors that promotes metastasis and represents a significant obstacle to successful cancer therapy. In response to hypoxia, cancer cells activate a transcriptional ... Read more >>

Antioxidants (Basel) (Antioxidants (Basel, Switzerland))
[2017, 6(2):]

Cited: 12 times

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PIM Kinase Inhibitors Kill Hypoxic Tumor Cells by Reducing Nrf2 Signaling and Increasing Reactive Oxygen Species.

Noel A Warfel, Alva G Sainz, Jin H Song, Andrew S Kraft,

Intratumoral hypoxia is a significant obstacle to the successful treatment of solid tumors, and it is highly correlated with metastasis, therapeutic resistance, and disease recurrence in cancer patients. As a result, there is an urgent need to develop effective therapies that target hypoxic cells within the tumor microenvironment. The Proviral ... Read more >>

Mol. Cancer Ther. (Molecular cancer therapeutics)
[2016, 15(7):1637-1647]

Cited: 9 times

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Insulin receptor substrate 1 is a substrate of the Pim protein kinases.

Jin H Song, Sathish K R Padi, Libia A Luevano, Mark D Minden, Daniel J DeAngelo, Gary Hardiman, Lauren E Ball, Noel A Warfel, Andrew S Kraft,

The Pim family of serine/threonine protein kinases (Pim 1, 2, and 3) contribute to cellular transformation by regulating glucose metabolism, protein synthesis, and mitochondrial oxidative phosphorylation. Drugs targeting the Pim protein kinases are being tested in phase I/II clinical trials for the treatment of hematopoietic malignancies. The goal of these ... Read more >>

Oncotarget (Oncotarget)
[2016, 7(15):20152-20165]

Cited: 9 times

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Small-Molecule NSC59984 Restores p53 Pathway Signaling and Antitumor Effects against Colorectal Cancer via p73 Activation and Degradation of Mutant p53.

Shengliang Zhang, Lanlan Zhou, Bo Hong, A Pieter J van den Heuvel, Varun V Prabhu, Noel A Warfel, Christina Leah B Kline, David T Dicker, Levy Kopelovich, Wafik S El-Deiry,

The tumor-suppressor p53 prevents cancer development via initiating cell-cycle arrest, cell death, repair, or antiangiogenesis processes. Over 50% of human cancers harbor cancer-causing mutant p53. p53 mutations not only abrogate its tumor-suppressor function, but also endow mutant p53 with a gain of function (GOF), creating a proto-oncogene that contributes to ... Read more >>

Cancer Res. (Cancer research)
[2015, 75(18):3842-3852]

Cited: 39 times

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PIM kinase (and Akt) biology and signaling in tumors.

Noel A Warfel, Andrew S Kraft,

The initiation and progression of human cancer is frequently linked to the uncontrolled activation of survival kinases. Two such pro-survival kinases that are commonly amplified in cancer are PIM and Akt. These oncogenic proteins are serine/threonine kinases that regulate tumorigenesis by phosphorylating substrates that control the cell cycle, cellular metabolism, ... Read more >>

Pharmacol. Ther. (Pharmacology & therapeutics)
[2015, 151:41-49]

Cited: 53 times

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CDK1 stabilizes HIF-1α via direct phosphorylation of Ser668 to promote tumor growth.

Noel A Warfel, Nathan G Dolloff, David T Dicker, Jozef Malysz, Wafik S El-Deiry,

Hypoxia-inducible factor 1 (HIF-1) is a major mediator of tumor physiology, and its activation is correlated with tumor progression, metastasis, and therapeutic resistance. HIF-1 is activated in a broad range of solid tumors due to intratumoral hypoxia or genetic alterations that enhance its expression or inhibit its degradation. As a ... Read more >>

Cell Cycle (Cell cycle (Georgetown, Tex.))
[2013, 12(23):3689-3701]

Cited: 38 times

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p21WAF1 and tumourigenesis: 20 years after.

Noel A Warfel, Wafik S El-Deiry,

PURPOSE OF REVIEW: This review provides an overview of the structure, regulation and physiological functions of p21, the product of the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene, with a focus on its dual role in promoting and repressing biological processes that are hallmarks of tumourigenesis. RECENT FINDINGS: Recent work has ... Read more >>

Curr Opin Oncol (Current opinion in oncology)
[2013, 25(1):52-58]

Cited: 150 times

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CTGF-mediated autophagy-senescence transition in tumor stroma promotes anabolic tumor growth and metastasis.

Varun V Prabhu, Noel A Warfel, Wafik S El-Deiry,

Cell Cycle (Cell cycle (Georgetown, Tex.))
[2012, 11(14):2592-2593]

Cited: 4 times

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Disruption of the interface between the pleckstrin homology (PH) and kinase domains of Akt protein is sufficient for hydrophobic motif site phosphorylation in the absence of mTORC2.

Noel A Warfel, Matt Niederst, Alexandra C Newton,

The pro-survival kinase Akt requires phosphorylation at two conserved residues, the activation loop site (Thr-308) and the hydrophobic motif site (Ser-473), for maximal activation. Previous reports indicate that mTORC2 is necessary for phosphorylation of the hydrophobic motif and that this site is not phosphorylated in cells lacking components of the ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2011, 286(45):39122-39129]

Cited: 22 times

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Pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP): a new player in cell signaling.

Noel A Warfel, Alexandra C Newton,

Precise balance between phosphorylation, catalyzed by protein kinases, and dephosphorylation, catalyzed by protein phosphatases, is essential for cellular homeostasis. Deregulation of this balance leads to pathophysiological states that drive diseases such as cancer, heart disease, and diabetes. The recent discovery of the PHLPP (pleckstrin homology domain leucine-rich repeat protein phosphatase) ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2012, 287(6):3610-3616]

Cited: 39 times

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Mislocalization of the E3 ligase, β-transducin repeat-containing protein 1 (β-TrCP1), in glioblastoma uncouples negative feedback between the pleckstrin homology domain leucine-rich repeat protein phosphatase 1 (PHLPP1) and Akt.

Noel A Warfel, Matt Niederst, Michael W Stevens, Paul M Brennan, Margaret C Frame, Alexandra C Newton,

The PH domain leucine-rich repeat protein phosphatase, PHLPP, plays a central role in controlling the amplitude of growth factor signaling by directly dephosphorylating and thereby inactivating Akt. The cellular levels of PHLPP1 have recently been shown to be enhanced by its substrate, activated Akt, via modulation of a phosphodegron recognized ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2011, 286(22):19777-19788]

Cited: 22 times

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Nelfinavir, A lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy, and apoptosis in vitro and in vivo.

Joell J Gills, Jaclyn Lopiccolo, Junji Tsurutani, Robert H Shoemaker, Carolyn J M Best, Mones S Abu-Asab, Jennifer Borojerdi, Noel A Warfel, Erin R Gardner, Matthew Danish, M Christine Hollander, Shigeru Kawabata, Maria Tsokos, William D Figg, Patricia S Steeg, Phillip A Dennis,

PURPOSE:The development of new cancer drugs is slow and costly. HIV protease inhibitors are Food and Drug Administration approved for HIV patients. Because these drugs cause toxicities that can be associated with inhibition of Akt, an emerging target in cancer, we assessed the potential of HIV protease inhibitors as anticancer ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2007, 13(17):5183-5194]

Cited: 161 times

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Importance of the stress kinase p38alpha in mediating the direct cytotoxic effects of the thalidomide analogue, CPS49, in cancer cells and endothelial cells.

Noel A Warfel, Erin R Lepper, Chunyu Zhang, William D Figg, Phillip A Dennis,

Thalidomide has gained renewed interest as a cancer therapeutic due to its potential antiangiogenic effects. The thalidomide analogues CPS11 and CPS49 are active in preclinical angiogenesis assays and xenograft model systems, but the biochemical basis for these observations is unclear.To address this question, we assessed the toxicity of these thalidomide ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2006, 12(11 Pt 1):3502-3509]

Cited: 12 times

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