Obesity, cholesterol, and clear-cell renal cell carcinoma (RCC)

Adv Cancer Res. 2010:107:39-56. doi: 10.1016/S0065-230X(10)07002-8.

Abstract

Multiple epidemiologic studies have linked the development of renal cancer to obesity. In this chapter, we begin with a review of selected population studies, followed by recent mechanistic discoveries that further link lipid deregulation to the RCC development. The upregulation of leptin and downregulation of adiponectin pathways in obesity fit well with our molecular understanding of RCC pathogenesis. In addition, two forms of hereditary RCC involve proteins, Folliculin and TRC8, that are positioned to coordinately regulate lipid and protein biosynthesis. Both of these biosynthetic pathways have important downstream consequences on HIF-1/2alpha levels and angiogenesis, key aspects in the disease pathogenesis. The role of lipid biology and its interface with protein translation regulation represents a new dimension in RCC research with potential therapeutic implications.

Publication types

  • Review

MeSH terms

  • Adiponectin / metabolism
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Carcinoma, Renal Cell / etiology*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cholesterol / metabolism*
  • Cytoskeletal Proteins
  • Estrone / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Kidney Neoplasms / etiology*
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism
  • Leptin / metabolism
  • Lipids / biosynthesis
  • Lipids / genetics
  • Molecular Chaperones
  • Neoplastic Syndromes, Hereditary / epidemiology
  • Neoplastic Syndromes, Hereditary / genetics
  • Neoplastic Syndromes, Hereditary / metabolism
  • Obesity / complications*
  • Obesity / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Sterol Regulatory Element Binding Proteins / metabolism

Substances

  • Adiponectin
  • Basic Helix-Loop-Helix Transcription Factors
  • Carrier Proteins
  • Cytoskeletal Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Leptin
  • Lipids
  • Molecular Chaperones
  • RNF139 protein, human
  • Receptors, Cell Surface
  • Sterol Regulatory Element Binding Proteins
  • VBP1 protein, human
  • endothelial PAS domain-containing protein 1
  • Estrone
  • Cholesterol