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Sweet Tooth of a Glucose Transporter: GLUT1 C‐terminal Phosphorylation and O‐GlcNacylation effect in Breast Cancer Cell Lines
Author(s) -
PadillaMeier Gay Pauline,
Mishra Suresh
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.717.14
Subject(s) - glut1 , glucose transporter , glucose transporter type 1 , cancer cell , phosphorylation , serine , glucose uptake , cancer , chemistry , biochemistry , biology , threonine , cancer research , microbiology and biotechnology , endocrinology , genetics , insulin
Cancer cells have altered metabolism that is largely dependent on aerobic glycolysis. In cancer cells elevated levels of glucose transporters (GLUT) facilitate the high glucose requirements of cancer cells. GLUT proteins allow for the passive transport across the plasma membrane down its concentration gradient. In various cancer tissues as well as human breast cancer cell lines elevated expression of GLUT1 has been reported. Another hallmark of cancer cells is hyper O‐GlcNacylation, which is a post translational modification (PTM) which adds a single N‐acetylglucosamine to either a serine or threonine residue. Only one O‐GlcNacylation site has been identified for GLUT1 (S465). The O‐GlcNacylation site of GLUT1 is in proximity of identified phosphorylation sites suggesting a possibility of interplay among the PTM sites of the C‐terminus. The aim our study is to discern if O‐GlcNacylation of GLUT1(S465) is affected by phosphorylation of neighboring residues and to determine if PTM of these sites regulate the function of GLUT1 and cancer cell metabolism. The single O‐GlcNacylation site in GLUT1 (S465) and neighboring serine/threonine residues were mutated and overexpressed in breast cancer cell lines. We investigated the molecular pathways involve in breast cancer cell metabolism and the effect of overexpression of GLUT1 variants. The GLUT1 variants showed altered levels of O‐GlcNac transferase, O‐GlcNacase and total O‐GlcNacylation of proteins in the cell. Breast cancer cell lines transfected with GLUT1 or it variants showed variable levels of glucose uptake. The results show that PTM of the c‐terminus of GLUT1 generally affects O‐GlcNacylation levels and metabolism of breast cancer cell lines.