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ZEB1 drives epithelial-to-mesenchymal transition in lung cancer

ZEB1 drives epithelial-to-mesenchymal transition in lung cancer
Written by Aaron Bolar on 2016-09-02


Increased expression of zinc finger E-box binding homeobox 1 (ZEB1) is associated with tumor grade and metastasis in lung cancer, likely due to its role as a transcription factor in epithelial-to-mesenchymal transition (EMT). Here, we modeled malignant transformation in human bronchial epithelial cells (HBECs) and determined that EMT and ZEB1 expression are early, critical events in lung cancer pathogenesis....(Read More)

Opposing actions of angiopoietin-2 on Tie2 signaling and FOXO1 activation

Opposing actions of angiopoietin-2 on Tie2 signaling and FOXO1 activation
Written by Aaron Bolar on 2016-08-23


Angiopoietin-2 (ANG2) regulates blood vessel remodeling in many pathological conditions through differential effects on Tie2 signaling. While ANG2 competes with ANG1 to inhibit Tie2, it can paradoxically also promote Tie2 phosphorylation (p-Tie2). A related paradox is that both inactivation and overactivation of Tie2 can result in vascular remodeling. Here, we reconciled these opposing actions of...(Read More)

ZEB1 drives epithelial-to-mesenchymal transition in lung cancer

ZEB1 drives epithelial-to-mesenchymal transition in lung cancer
Written by Aaron Bolar on 2016-08-13


Increased expression of zinc finger E-box binding homeobox 1 (ZEB1) is associated with tumor grade and metastasis in lung cancer, likely due to its role as a transcription factor in epithelial-to-mesenchymal transition (EMT). Here, we modeled malignant transformation in human bronchial epithelial cells (HBECs) and determined that EMT and ZEB1 expression are early, critical events in lung cancer pathogenesis....(Read More)

Loss of ABCG1 influences regulatory T cell differentiation and atherosclerosis

Loss of ABCG1 influences regulatory T cell differentiation and atherosclerosis
Written by Aaron Bolar on 2016-08-03


ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol accumulation and alters T cell homeostasis, which may contribute to progression of atherosclerosis. Here, we investigated how the selective loss of ABCG1 in T cells impacts atherosclerosis in LDL receptor–deficient (LDLR-deficient) mice, a model of the disease. In LDLR-deficient mice fed a high-cholesterol diet, T cell–specific...(Read More)

Schlafen 4–expressing myeloid-derived suppressor cells are induced during murine gastric metaplasia

Schlafen 4–expressing myeloid-derived suppressor cells are induced during murine gastric metaplasia
Written by Aaron Bolar on 2016-07-24


Chronic Helicobacter pylori infection triggers neoplastic transformation of the gastric mucosa in a small subset of patients, but the risk factors that induce progression to gastric metaplasia have not been identified. Prior to cancer development, the oxyntic gastric glands atrophy and are replaced by metaplastic cells in response to chronic gastritis. Previously, we identified schlafen 4 (Slfn4)...(Read More)

Natural allelic variation of the IL-21 receptor modulates ischemic stroke infarct volume

Natural allelic variation of the IL-21 receptor modulates ischemic stroke infarct volume
Written by Aaron Bolar on 2016-07-14


Risk for ischemic stroke has a strong genetic basis, but heritable factors also contribute to the extent of damage after a stroke has occurred. We previously identified a locus on distal mouse chromosome 7 that contributes over 50% of the variation in postischemic cerebral infarct volume observed between inbred strains. Here, we used ancestral haplotype analysis to fine-map this locus to 12 candidate...(Read More)

p66Shc regulates renal vascular tone in hypertension-induced nephropathy

p66Shc regulates renal vascular tone in hypertension-induced nephropathy
Written by Aaron Bolar on 2016-07-04


Renal preglomerular arterioles regulate vascular tone to ensure a large pressure gradient over short distances, a function that is extremely important for maintaining renal microcirculation. Regulation of renal microvascular tone is impaired in salt-sensitive (SS) hypertension–induced nephropathy, but the molecular mechanisms contributing to this impairment remain elusive. Here, we assessed the...(Read More)

CKAP4 is a Dickkopf1 receptor and is involved in tumor progression

CKAP4 is a Dickkopf1 receptor and is involved in tumor progression
Written by Aaron Bolar on 2016-06-24


Dickkopf1 (DKK1) is a secretory protein that antagonizes oncogenic Wnt signaling by binding to the Wnt coreceptor low-density lipoprotein receptor–related protein 6 (LRP6). DKK1 may also regulate its own signaling to promote cancer cell proliferation, but the mechanism is not understood. Here, we identified cytoskeleton-associated protein 4 (CKAP4) as a DKK1 receptor and evaluated CKAP4-mediated...(Read More)

CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer

CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer
Written by Aaron Bolar on 2016-06-14


Small-cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer with limited treatment options. CD47 is a cell-surface molecule that promotes immune evasion by engaging signal-regulatory protein alpha (SIRPα), which serves as an inhibitory receptor on macrophages. Here, we found that CD47 is highly expressed on the surface of human SCLC cells; therefore, we investigated CD47-blocking...(Read More)





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