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PGC1?: Friend or Foe in Cancer?

ABSTRACT: The PGC1 family (Peroxisome proliferator-activated receptor ? (PPAR?) coactivators) of transcriptional coactivators are considered master regulators of mitochondrial biogenesis and function. The PGC1? isoform is expressed especially in metabolically active tissues, such as the liver, kidneys and brain, and responds to energy-demanding situations. Given the altered and highly adaptable metabolism of tumor cells, it is of interest to investigate PGC1? in cancer. Both high and low levels of PGC1? expression have been reported to be associated with cancer and worse prognosis, and PGC1? has been attributed with oncogenic as well as tumor suppressive features. Early in carcinogenesis PGC1? may be downregulated due to a protective anticancer role, and low levels likely reflect a glycolytic phenotype. We suggest mechanisms of PGC1? downregulation and how these might be connected to the increased cancer risk that obesity is now known to entail. Later in tumor progression PGC1? is often upregulated and is reported to contribute to increased lipid and fatty acid metabolism and/or a tumor cell phenotype with an overall metabolic plasticity that likely supports drug resistance as well as metastasis. We conclude that in cancer PGC1? is neither friend nor foe, but rather the obedient servant reacting to metabolic and environmental cues to benefit the tumor cell.

SUBMITTER: Mastropasqua F

PROVIDER: S-EPMC5793199 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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PGC1α: Friend or Foe in Cancer?

Mastropasqua Francesca F Girolimetti Giulia G Shoshan Maria M

Genes 20180122 1

The PGC1 family (Peroxisome proliferator-activated receptor γ (PPARγ) coactivators) of transcriptional coactivators are considered master regulators of mitochondrial biogenesis and function. The PGC1α isoform is expressed especially in metabolically active tissues, such as the liver, kidneys and brain, and responds to energy-demanding situations. Given the altered and highly adaptable metabolism of tumor cells, it is of interest to investigate PGC1α in cancer. Both high and low levels of PGC1α e ...[more]

PMID: 29361779

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Project description:Cancer remains the leading cause of death worldwide with close to 10 million deaths reported annually. Due to growth of the advanced age cohort in our population, it is predicted that the number of new cancer cases diagnosed between now until 2035 is to reach potentially 24 million individuals, a staggering increase in a relatively short time period. For many solid tumors, surgical resection along with chemotherapy is the best available approach to a potential cure which leads to almost 80% of cancer patients undergoing at least one surgical procedure during the course of their disease. During surgical intervention, the exposure to general anesthesia can be lengthy, complex and often involves various modalities resulting in an important question as to the role, if any, anesthesia may play in primary recurrence or metastatic conversion. Many components of the stress and inflammatory responses exhibited in the perioperative period can contribute to cancer growth and invasion. The agents used to induce and maintain general anesthesia have variable interactions with the immune and neuroendocrine systems and can influence the stress response during surgery. Thus, debating the best type of anesthesia that would help to attenuate sympathetic and/or pro-inflammatory responses while modulating cytokine release and transcription factors/oncogenes remains at the forefront. This may affect inducible cancer cell survival and migratory abilities not only intra-operatively, but also during the immediate post-operative phase of recovery. The ultimate question becomes how and whether the choice of anesthesia may influence the outcomes of cancer surgery with two major approaches being considered, i.e., regional and general anesthesia as well as the various hypnotics, analgesics and sympatholytics commonly used. In this review, we will address the latest information as to the role that anesthesia may play during cancer surgery with specific focus on primary recurrence and metastasis.

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PGC1?: Friend or Foe in Cancer?

Publications

PGC1α: Friend or Foe in Cancer?

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