PTEN regulates plasma membrane expression of glucose transporter 1 and glucose uptake in thyroid cancer cells

Glucose represents an important source of energy for the cells. Proliferating cancer cells consume elevated quantity of glucose, which is converted into lactate regardless of the presence of oxygen. This phenomenon, known as the Warburg effect, has been proven to be useful for imaging metabolically active tumours in cancer patients by 18F-fluorodeoxyglucose positron emission tomography (FDG–PET). Glucose is internalised in the cells by glucose transporters (GLUTs) belonging to the GLUT family. GLUT1 (SLC2A1) is the most prevalent isoform in more aggressive and less differentiated thyroid cancer histotypes. In a previous work, we found that loss of expression of PTEN was associated with increased expression of GLUT1 on the plasma membrane (PM) and probability of detecting thyroid incidentalomas by FDG–PET. Herein, we investigated the molecular pathways that govern the expression of GLUT1 on the PM and the glucose uptake in WRO (expressing WT PTEN) and FTC133 (PTEN null) follicular thyroid cancer cells cultured under glucose-depleted conditions. The membrane expression of GLUT1 was enhanced in glucose-deprived cells. Through genetic manipulations of PTEN expression, we could demonstrate that the lack of this oncosuppressor has a dominant effect on the membrane expression of GLUT1 and glucose uptake. We conclude that loss of function of PTEN increases the probability of cancer detection by FDG–PET or other glucose-based imaging diagnosis.

Download Full-text

446 The Oncosuppressor PTEN Regulates the Membrane Expression of GLUT1 in Thyroid Cancer Cells – Implication for Diagnosis With FDG-PET

European Journal of Cancer ◽

10.1016/s0959-8049(12)71121-8 ◽

2012 ◽

Vol 48 ◽

pp. S107

Author(s):

F. Morani ◽

L. Pagano ◽

F. Prodam ◽

M.T. Sama ◽

C. Peracchio ◽

...

Keyword(s):

Thyroid Cancer ◽

Cancer Cells ◽

Fdg Pet ◽

Membrane Expression ◽

Thyroid Cancer Cells

Download Full-text

Glucose-dependent glucose transporter 1 expression and its impact on viability of thyroid cancer cells

Oncology Reports ◽

10.3892/or.2014.3673 ◽

2014 ◽

Vol 33 (2) ◽

pp. 913-920 ◽

Cited By ~ 9

Author(s):

PAWEŁ JÓŹWIAK ◽

ANNA KRZEŚLAK ◽

MAGDALENA BRYŚ ◽

ANNA LIPIŃSKA

Keyword(s):

Thyroid Cancer ◽

Cancer Cells ◽

Glucose Transporter ◽

Glucose Transporter 1 ◽

Thyroid Cancer Cells

Download Full-text

RAPID COMMUNICATION: Predominant Intracellular Overexpression of the Na+/I− Symporter (NIS) in a Large Sampling of Thyroid Cancer Cases

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.6.7746 ◽

2001 ◽

Vol 86 (6) ◽

pp. 2697-2700 ◽

Cited By ~ 1

Author(s):

Orsolya Dohán ◽

Zubair Baloch ◽

Zsuzsa Bánrévi ◽

Virginia Livolsi ◽

Nancy Carrasco

Keyword(s):

Plasma Membrane ◽

Thyroid Cancer ◽

Protein Expression ◽

Cancer Cells ◽

Malignant Transformation ◽

Thyroid Tissue ◽

Rapid Communication ◽

High Affinity ◽

Intracellular Compartments ◽

Thyroid Cancer Cells

ABSTRACT Here we report the analysis of the Na+/I− symporter (NIS) protein expression in 57 thyroid cancer samples by immunohistochemistry with high-affinity anti-NIS Abs. As many as 70% of these samples exhibited increased NIS expression with respect to the normal surrounding thyroid tissue. Most significantly, NIS was located in these samples either in both the plasma membrane and intracellular compartments simultaneously, or exclusively in intracellular compartments. This suggests that NIS is clearly expressed or even overexpressed in most thyroid cancer cells, but malignant transformation in some of these cells interferes either with the proper targeting of NIS to the plasma membrane, or with the mechanisms that retain NIS in the plasma membrane after it has been targeted. The results further indicate that, in addition to indicating NIS expression in cases where it is absent (∼30%), improvements in 131I radioablation therapy might result from promoting targeting of NIS to the plasma membrane in the majority (∼70%) of thyroid cancers.

Download Full-text

Tmod3 Phosphorylation Mediates AMPK-Dependent GLUT4 Plasma Membrane Insertion in Myoblasts

Frontiers in Endocrinology ◽

10.3389/fendo.2021.653557 ◽

2021 ◽

Vol 12 ◽

Author(s):

Man Mohan Shrestha ◽

Chun-Yan Lim ◽

Xuezhi Bi ◽

Robert C. Robinson ◽

Weiping Han

Keyword(s):

Plasma Membrane ◽

Glucose Uptake ◽

Glucose Transporter ◽

Fluorescent Microscopy ◽

Membrane Insertion ◽

Glut4 Translocation ◽

Loss Of Function ◽

Microscopy Imaging ◽

Actin Remodeling ◽

Capping Protein

Insulin and muscle contractions mediate glucose transporter 4 (GLUT4) translocation and insertion into the plasma membrane (PM) for glucose uptake in skeletal muscles. Muscle contraction results in AMPK activation, which promotes GLUT4 translocation and PM insertion. However, little is known regarding AMPK effectors that directly regulate GLUT4 translocation. We aim to identify novel AMPK effectors in the regulation of GLUT4 translocation. We performed biochemical, molecular biology and fluorescent microscopy imaging experiments using gain- and loss-of-function mutants of tropomodulin 3 (Tmod3). Here we report Tmod3, an actin filament capping protein, as a novel AMPK substrate and an essential mediator of AMPK-dependent GLUT4 translocation and glucose uptake in myoblasts. Furthermore, Tmod3 plays a key role in AMPK-induced F-actin remodeling and GLUT4 insertion into the PM. Our study defines Tmod3 as a key AMPK effector in the regulation of GLUT4 insertion into the PM and glucose uptake in muscle cells, and offers new mechanistic insights into the regulation of glucose homeostasis.

Download Full-text

Hypoxia induces the translocation of glucose transporter 1 to the plasma membrane in vascular endothelial cells

The Journal of Physiological Sciences ◽

10.1186/s12576-020-00773-y ◽

2020 ◽

Vol 70 (1) ◽

Cited By ~ 1

Author(s):

Abdullah Al Mamun ◽

Hisaki Hayashi ◽

Aya Yamamura ◽

Md Junayed Nayeem ◽

Motohiko Sato

Keyword(s):

Endothelial Cells ◽

Plasma Membrane ◽

Cell Surface ◽

Glucose Uptake ◽

Katp Channel ◽

Glucose Transporter ◽

Umbilical Vein ◽

Cell Surface Expression ◽

Glucose Transporter 1 ◽

Intracellular Atp

Abstract Glucose uptake and adenosine triphosphate (ATP) generation are important for the survival and growth of endothelial cells. An increase of glucose uptake under hypoxia was previously shown to be associated with the increased expression of glucose transporters (GLUTs). However, the regulation of GLUT trafficking to the cell surface has not been examined in detail. Here, we report the characterization of GLUT1 translocation to the plasma membrane during hypoxia in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were exposed to hypoxia (1% O2) for 12 h, which significantly induced GLUT1 expression and translocation to the plasma membrane. GLUT1 translocation was associated with a decrease of intracellular ATP by hypoxia. Decreasing ATP levels with antimycin-A and 2-deoxyglucose induced GLUT1 translocation under normoxia. The induction of hypoxia-inducible factor-1α under normoxia did not influence the cell surface expression of GLUT1 or cellular ATP concentration. Interestingly, the translocation of GLUT1 induced by hypoxia was inhibited by the ATP-sensitive potassium (KATP) channel inhibitor glibenclamide, while the mitochondrial KATP channel inhibitor 5-HD did not influence GLUT1 translocation during hypoxia. These observations indicate that a decrease of intracellular ATP triggers GLUT1 translocation to the plasma membrane and is mediated by KATP channels, which would contribute to glucose uptake in HUVECs during hypoxia.

Download Full-text

IncRNA MAPKAPK5-AS1 promotes proliferation and migration of thyroid cancer cell lines by targeting miR-519e-5p/YWHAH

European Journal of Histochemistry ◽

10.4081/ejh.2020.3177 ◽

2020 ◽

Vol 64 (4) ◽

Author(s):

Yan Zhou ◽

Shanshan Liu ◽

Yan Luo ◽

Meiying Zhang ◽

Xueling Jiang ◽

...

Keyword(s):

Thyroid Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Critical Role ◽

Endocrine System ◽

Migration And Invasion ◽

Loss Of Function ◽

And Migration ◽

Thyroid Cancer Cells ◽

Proliferation And Migration

Thyroid cancer is a common malignant tumour of the endocrine system and ranks ninth in cancer incidence worldwide. An extensive body of evidence has demonstrated that lncRNAs play a critical role in the progression of thyroid cancer. The lncRNA MAPKAPK5-AS1 has been reported to be abnormally expressed and to play a role in the development of various human cancers. However, MAPKAPK5-AS1’s potential role in thyroid cancer progression remains unknown. The objective of our study was to explore the role and mechanism of MAPKAPK5-AS1 in thyroid cancer cells and provide a potential target for its biological diagnosis and treatment. We transfected sh-MAPKAPK5-AS1 and sh-NC into BCPAP and TPC-1 cells for loss-of-function assays. Results of RT-qPCR analysis demonstrated that MAPKAPK5-AS1 was more highly expressed in thyroid cancer cells compared to normal cells. Functional assays demonstrated that interfering with the expression of MAPKAPK5-AS1 notably repressed proliferation and invasion and accelerated apoptosis of BCPAP and TPC-1 cells. Mechanistically, we found that miR-519e-5p was negatively regulated by MAPKAPK5-AS1 and that tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) was a target of miR-519e-5p. Additionally, rescue assays demonstrated that downregulation of MAPKAPK5-AS1 expression inhibited cell proliferation, migration, and invasion and promoted apoptosis by sponging miR-519e-5p, thereby increasing YWHAH expression. Ultimately, our study revealed that MAPKAPK5-AS1 promotes proliferation and migration of thyroid cancer cells by targeting the miR-519e-5p/YWHAH axis, which provides novel insight into the development and progression of thyroid cancer.

Download Full-text

Regulation of GLUT1-mediated glucose uptake by PKCλ–PKCβII interactions in 3T3-L1 adipocytes

Biochemical Journal ◽

10.1042/bj20040797 ◽

2004 ◽

Vol 384 (2) ◽

pp. 349-355 ◽

Cited By ~ 10

Author(s):

Remko R. BOSCH ◽

Merlijn BAZUINE ◽

Paul N. SPAN ◽

Peter H. G. M. WILLEMS ◽

André J. OLTHAAR ◽

...

Keyword(s):

Plasma Membrane ◽

Protein Kinase ◽

Glucose Uptake ◽

Glucose Transport ◽

Glucose Transporter ◽

Mitogen Activated Protein Kinase ◽

Glucose Transporter 1 ◽

Protein Levels ◽

Mitogen Activated Protein ◽

Pkc Protein Kinase C

Members of the PKC (protein kinase C) superfamily play key regulatory roles in glucose transport. How the different PKC isotypes are involved in the regulation of glucose transport is still poorly defined. PMA is a potent activator of conventional and novel PKCs and PMA increases the rate of glucose uptake in many different cell systems. In the present study, we show that PMA treatment increases glucose uptake in 3T3-L1 adipocytes by two mechanisms: a mitogen-activated protein kinase kinase-dependent increase in GLUT1 (glucose transporter 1) expression levels and a PKCλ-dependent translocation of GLUT1 towards the plasma membrane. Intriguingly, PKCλ co-immunoprecipitated with PKCβII and did not with PKCβI. Previously, we have described that down-regulation of PKCβII protein levels or inhibiting PKCβII by means of the myristoylated PKCβC2–4 peptide inhibitor induced GLUT1 translocation towards the plasma membrane in 3T3-L1 adipocytes. Combined with the present findings, these results suggest that the liberation of PKCλ from PKCβII is an important factor in the regulation of GLUT1 distribution in 3T3-L1 adipocytes.

Download Full-text