Regulators of glucose uptake in thyroid cancer cell lines

Abstract

Thyroid cancer is the most common sort of endocrine-related cancer with more prevalent in women and elderly individuals which has quickly widespread expansion in worldwide over the recent decades. Common features of malignant thyroid cells are to have accelerated metabolism and increased glucose uptake to optimize their energy supply which provides a fundamental advantage for growth. In tumor cells the retaining of required energy charge for cell survival is imperative, indeed glucose transporters are enable of promoting of this task. According to this relation it has been reported the upregulation of glucose transporters in various types of cancers. Human studies indicated that poor survival can be occurred following the high levels of GLUT1 expression in tumors. GLUT-1 and GLUT3 are the glucose transporters which seems to be mainly engaged with the oncogenesis of thyroid cancer and their expression in malignant tissues is much more than in the normal one. They are promising targets for the advancement of anticancer strategies. The lack of oncosuppressors have dominant effect on the membrane expression of GLUT1 and glucose uptake. Overexpression of hypoxia inducible factors have been additionally connected with distant metastasis in thyroid cancers which mediates transcriptional regulation of glycolytic genes including GLUT1 and GLUT3. Though the physiological role of the thyroid gland is well illustrated, but the metabolic regulations in thyroid cancer remain evasive. In this study we discuss proliferation pathways of the key regulators and signaling molecules such as PI3K-Akt, HIF-1, MicroRNA, PTEN, AMPK, BRAF, c-Myc, TSH, Iodide and p53 which includes in the regulation of GLUTs in thyroid cancer cells. Incidence of deregulations in cellular energetics and metabolism are the most serious signs of cancers. In conclusion, understanding the mechanisms of glucose transportation in normal and pathologic thyroid tissues is critically important and could provide significant insights in science of diagnosis and treatment of thyroid disease.

The crosstalk between HIFs and mitochondrial dysfunctions in cancer development

“…HIF-1α also regulates tumor growth by adjusting anaerobic and aerobic oxidation of glucose 46 . Glycolytic reprogramming is a key feature of metabolic reprogramming in tumors; thus, HIF-1α regulates glycolytic reprogramming by directly stimulating the transcription of all 12 enzymes that are necessary for glycolysis 47 , 48 . As an example, neuronal PAS domain protein 2 (NPAS2) upregulates glycolytic genes GLUT1 , HK2 , ALDOA , GPI , MCT4 , ENO2 , and PKM2 by transcriptional upregulation of HIF-1α in hepatocellular carcinoma (HCC) 49 .…”

Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases

“…This location provides melatonin with significant advantages in terms of its ability to control cancer cell metabolism as well as relieving cells, when necessary, of undo oxidative stress. Its ability to both modulate glucose uptake and its intracellular metabolism also makes it an important agent in resisting cancer since these cells typically have a “sweet tooth” and require excessive amounts of glucose to sustain their growth [ 87 , 88 ]. Having identified these actions, however, the reader may be left with the impression that these functions are universal and unwavering under all metabolic circumstances.…”

PRDM14 mediates chemosensitivity and glycolysis in drug‑resistant A549/cisplatin cells and their progenitor A549 human lung adenocarcinoma cells

“…The metabolic priorities of cancer cells differ from those of normal cells, thus providing a new therapeutic window; the Warburg effect, also termed glycolysis, is characterized by high glucose uptake and lactate release, and is considered to be a hallmark of prostate cancer ( 31 ). This metabolic adaptation benefits cancer cells in surviving through hypoxic conditions, which are common in tumors, and supports their anabolic requirements ( 32 ). Elaborating the central role of PRDM14 in the glycolysis of DDP-resistant lung cancer cells is an important outcome of the present study.…”