Dataset Information

Metabolic Alterations in Cancer Cells and the Emerging Role of Oncometabolites as Drivers of Neoplastic Change.

ABSTRACT: The mitochondrion is an important organelle and provides energy for a plethora of intracellular reactions. Metabolic dysregulation has dire consequences for the cell, and alteration in metabolism has been identified in multiple disease states-cancer being one. Otto Warburg demonstrated that cancer cells, in the presence of oxygen, undergo glycolysis by reprogramming their metabolism-termed "aerobic glycolysis". Alterations in metabolism enable cancer cells to gain a growth advantage by obtaining precursors for macromolecule biosynthesis, such as nucleic acids and lipids. To date, several molecules, termed "oncometabolites", have been identified to be elevated in cancer cells and arise from mutations in nuclear encoded mitochondrial enzymes. Furthermore, there is evidence that oncometabolites can affect mitochondrial dynamics. It is believed that oncometabolites can assist in reprogramming enzymatic pathways and providing cancer cells with selective advantages. In this review, we will touch upon the effects of normal and aberrant mitochondrial metabolism in normal and cancer cells, the advantages of metabolic reprogramming, effects of oncometabolites on metabolism and mitochondrial dynamics and therapies aimed at targeting oncometabolites and metabolic aberrations.

SUBMITTER: Zhou Z

PROVIDER: S-EPMC5789326 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Metabolic Alterations in Cancer Cells and the Emerging Role of Oncometabolites as Drivers of Neoplastic Change.

Zhou Zhengqiu Z Ibekwe Elochukwu E Chornenkyy Yevgen Y

Antioxidants (Basel, Switzerland) 20180117 1

The mitochondrion is an important organelle and provides energy for a plethora of intracellular reactions. Metabolic dysregulation has dire consequences for the cell, and alteration in metabolism has been identified in multiple disease states-cancer being one. Otto Warburg demonstrated that cancer cells, in the presence of oxygen, undergo glycolysis by reprogramming their metabolism-termed "aerobic glycolysis". Alterations in metabolism enable cancer cells to gain a growth advantage by obtaining ...[more]

PMID: 29342092

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Project description:BackgroundCervical carcinomas are second most frequent type of women cancer. Success in diagnostics of this disease is due to the use of Pap-test (cytological smear analysis). However Pap-test gives significant portion of both false-positive and false-negative conclusions. Amendments of the diagnostic procedure are desirable. Aetiological role of papillomaviruses in cervical cancer is established while the role of cellular gene alterations in the course of tumor progression is less clear. Several research groups including us have recently named the protein p16INK4a as a possible diagnostic marker of cervical cancer. To evaluate whether the specificity of p16INK4a expression in dysplastic and neoplastic cervical epithelium is sufficient for such application we undertook a broader immunochistochemical registration of this protein with a highly p16INK4a-specific monoclonal antibody.MethodsParaffin-embedded samples of diagnostic biopsies and surgical materials were used. Control group included vaginal smears of healthy women and biopsy samples from patients with cervical ectopia. We examined 197 samples in total. Monoclonal antibody E6H4 (MTM Laboratories, Germany) was used.ResultsIn control samples we did not find any p16INK4a-positive cells. Overexpression of p16INK4a was detected in samples of cervical dysplasia (CINs) and carcinomas. The portion of p16INK4a-positive samples increased in the row: CIN I - CIN II - CIN III - invasive carcinoma. For all stages the samples were found to be heterogeneous with respect to p16INK4a-expression. Every third of CINs III and one invasive squamous cell carcinoma (out of 21 analyzed) were negative.ConclusionsOverexpression of the protein p16INK4a is typical for dysplastic and neoplastic epithelium of cervix uteri. However p16INK4a-negative CINs and carcinomas do exist. All stages of CINs and carcinomas analyzed are heterogeneous with respect to p16INK4a expression. So p16INK4a-negativity is not a sufficient reason to exclude a patient from the high risk group. As far as normal cervical epithelium is p16INK4a-negative and the ratio p16INK4a-positive/ p16INK4a-negative samples increases at the advanced stages application of immunohisto-/cytochemical test for p16INK4a may be regarded as a supplementary test for early diagnostics of cervical cancer.

Dataset Information

Metabolic Alterations in Cancer Cells and the Emerging Role of Oncometabolites as Drivers of Neoplastic Change.

Publications

Metabolic Alterations in Cancer Cells and the Emerging Role of Oncometabolites as Drivers of Neoplastic Change.

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