P-LAP/IRAP-induced cell proliferation and glucose uptake in endometrial carcinoma cells via insulin receptor signaling

Shibata, Kiyosumi; Kajiyama, Hiroaki; Ino, Kazuhiko; Nawa, Akihiro; Nomura, Seiji; Mizutani, Shigehiko; Kikkawa, Fumitaka

doi:10.1186/1471-2407-7-15

Cited by 18 publications

(9 citation statements)

References 21 publications

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“…In contrast to a basal expression of GLUT4 detected in non-tumorigenic human and rat ovary (Shibata et al, 2007), rat liver (Abel et al, 2001), and rat kidney (supplementary material), Western blotting (Fig. 3) and kinetic analysis (data not shown) revealed that GLUT4 was expressed at negligible levels in both AS-30D hepatocarcinoma and HeLa cells.…”

Section: Low Glut4 Expression In As-30d and Hela Carcinomascontrasting

confidence: 80%

Kinetics of transport and phosphorylation of glucose in cancer cells

Rodrı́guez-Enrı́quez

Marín‐Hernández

Gallardo‐Pérez

et al. 2009

Journal Cellular Physiology

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Metabolic control analysis of tumor glycolysis has indicated that hexokinase (HK) and glucose transporter (GLUT) exert the main flux control (71%). To understand why they are the main controlling steps, the GLUT and HK kinetics and the contents of GLUT1, GLUT2, GLUT3, GLUT4, HKI, and HKII were analyzed in rat hepatocarcinoma AS-30D and HeLa human cervix cancer. An improved protocol to determine the kinetic parameters of GLUT was developed with D-[2-(3)H-glucose] as physiological substrate. Kinetic analysis revealed two components at low- and high-glucose concentrations in both tumor cells. At low glucose and 37 degrees C, the V(max) was 55 +/- 20 and 17.2 +/- 6 nmol (min x mg protein)(-1), whereas the K(m) was 0.52 +/- 0.7 and 9.3 +/- 3 mM for hepatoma and HeLa cells, respectively. GLUT activity was partially inhibited by cytochalasin B (IC(50) = 0.44 +/- 0.1; K(i) = 0.3 +/- 0.1 microM) and phloretin (IC(50) = 8.7 microM) in AS-30D hepatocarcinoma. At physiological glucose, GLUT1 and GLUT3 were the predominant active isoforms in HeLa cells and AS-30D cells, respectively. HK activity in HeLa cells was much lower (60 mU/mg protein) than that in AS-30D cells (700 mU/mg protein), but both HKs were strongly inhibited by G6P. HKII was the predominant isoform in AS-30D carcinoma and HeLa cells. The much lower GLUT V(max) and catalytic efficiency (V(max)/K(m)) values in comparison to those of G6P-sensitive HK suggested the transporter exerts higher control on the glycolytic flux than HK in cancer cells. Thus, GLUT seems a more adequate therapeutic target.

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Section: Low Glut4 Expression In As-30d and Hela Carcinomascontrasting

confidence: 80%

Kinetics of transport and phosphorylation of glucose in cancer cells

Rodrı́guez-Enrı́quez

Marín‐Hernández

Gallardo‐Pérez

et al. 2009

Journal Cellular Physiology

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“…Interestingly, the angiotensin-converting enzyme gene, which is also a key component in the renin-angiotensin system, was widely reported to be associated with psoriasis (Weger et al, 2007;Veletza et al, 2008;Lamba et al, 2011) and lends further support to involvement of the renin-angiotensin system in the development of psoriasis. Moreover, LNPEP has also been implicated in diabetes, as it affects glucose uptake via the interaction of insulin receptor signaling with the insulinresponsive glucose transporter GLUT4 (Shibata et al, 2007). It was reported that genetic variants in LNPEP were associated with biological effects on vasopressin clearance and serum sodium regulation (Nakada et al, 2011), which are generally accepted as key biological factors in hypertension, diabetes, and other metabolic phenotypes (Enhorning et al, 2009;Patel and Mehta, 2012).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Missense Variant in LNPEP that Confers Psoriasis Risk

Cheng

Zuo

et al. 2014

Journal of Investigative Dermatology

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Psoriasis is a chronic inflammatory disease with a complex genetic architecture. To further advance gene discovery, we extended our genome-wide association study data set of 1,139 cases and 2,234 controls and replicated two independent cohorts of 7,200 cases and 10,491 controls. We identified the missense variant rs2303138 (p.Ala763Thr) within the LNPEP gene associated with psoriasis (Pcombined=1.83 × 10(-13), odds ratio=1.16) and validated four previously reported genes: IL28RA, NFKBIA, TRAF3IP2, and CARD14 (9.74 × 10(-11)P9.37 × 10(-5)), which confirmed the involvement of the nuclear factor-κB signaling pathway in psoriasis pathogenesis. LNPEP, also named insulin-responsive aminopeptidase, was identified as an angiotensin IV receptor. Protein function prediction suggested that this missense variant of LNPEP was most likely deleterious. Expression analysis showed that LNPEP was significantly downregulated in psoriatic lesions compared with the control skin (P=1.44 × 10(-6)) and uninvolved patient skin (P=2.95 × 10(-4)). Pathway analysis indicated that LNPEP was involved in the renin-angiotensin system, which also has a key role in cardiovascular disease and diabetes. These results provided genetic evidence that psoriasis might share common mechanisms with hypertension and diabetes, which was consistent with clinical observations. Our study identified a genetic susceptibility factor and provided genetic evidence of insight into psoriasis pathogenesis with the involvement of the renin-angiotensin system pathway.

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“…Glucose transporter (GLUT) 1, 4, and 8 expression is upregulated in endometrial cancer cells, and may be linked to tumor progression and differentiation (Goldman et al 2006, Shibata et al 2007. Previous, smaller, prospective (Furberg & Thune 2003), and case-control (Levran et al 1984, Rutanen et al 1993 studies have also observed increased risks associated with high glucose levels.…”

Section: Discussionmentioning

confidence: 99%

Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Cust¹,

Kaaks²,

Friedenreich³

et al. 2007

Endocr Relat Cancer

118

111

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To clarify the role of metabolic factors in endometrial carcinogenesis, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), and examined the relation between prediagnostic plasma lipids, lipoproteins, and glucose, the metabolic syndrome (MetS; a cluster of metabolic factors) and endometrial cancer risk. Among pre-and postmenopausal women, 284 women developed endometrial cancer during follow-up. Using risk set sampling, 546 matched control subjects were selected. From conditional logistic regression models, high-density lipoprotein cholesterol (HDL-C) levels were inversely associated with risk body mass index (BMI)-adjusted relative risk (RR) for top versus bottom quartile 0.61 (95% confidence intervals (CI) 0.38-0.97), P trend Z0.02). Glucose levels were positively associated with risk (BMI-adjusted RR top versus bottom quartile 1.69 (95% CI 0.99-2.90), P trend Z0.03), which appeared stronger among postmenopausal women (BMI-adjusted RR top versus bottom tertile 2.61 (95% CI 1.46-4.66), P trend Z0.0006, P heterogeneity Z0.13) and never-users of exogenous hormones (P heterogeneity Z0.005 for oral contraceptive (OC) use and 0.05 for hormone replacement therapy-use). The associations of HDL-C and glucose with risk were no longer statistically significant after further adjustment for obesity-related hormones. Plasma total cholesterol, Low-density lipoprotein cholesterol (LDL-C), and triglycerides were not significantly related to overall risk. The presence of MetS was associated with risk (RR 2.12 (95% CI 1.51-2.97)), which increased with the number of MetS factors (P trend Z0.02). An increasing number of MetS factors other than waist circumference, however, was marginally significantly associated with risk only in women with waist circumference above the median (P interaction Z0.01). None of the associations differed significantly by fasting status. These findings suggest that metabolic abnormalities and obesity may act synergistically to increase endometrial cancer risk.

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P-LAP/IRAP-induced cell proliferation and glucose uptake in endometrial carcinoma cells via insulin receptor signaling

Cited by 18 publications

References 21 publications

Kinetics of transport and phosphorylation of glucose in cancer cells

Kinetics of transport and phosphorylation of glucose in cancer cells

Identification of a Missense Variant in LNPEP that Confers Psoriasis Risk

Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

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