Identification of signaling pathways associated with cancer protection in Laron syndrome

Lena Lapkina-Gendler, Itai Rotem, Metsada Pasmanik-Chor, David Gurwitz, Rive Sarfstein, Zvi Laron, Haim Werner

Research output: Contribution to journalArticlepeer-review

Abstract

The growth hormone (GH)-insulin-like growth factor-1 (IGF1) pathway emerged in recent years as a critical player in cancer biology. Enhanced expression or activation of specific components of the GH-IGF1 axis, including the IGF1 receptor (IGF1R), is consistently associated with a transformed phenotype. Recent epidemiological studies have shown that patients with Laron syndrome (LS), the best-characterized entity among the congenital IGF1 deficiencies, seem to be protected from cancer development. To identify IGF1-dependent genes and signaling pathways associated with cancer protection in LS, we conducted a genome-wide analysis using immortalized lymphoblastoid cells derived from LS patients and healthy controls of the same gender, age range, and ethnic origin. Our analyses identified a collection of genes that are either over- or under-represented in LS-derived lymphoblastoids. Gene differential expression occurs in several gene families, including cell cycle, metabolic control, cytokine-cytokine receptor interaction, Jak-STAT signaling, and PI3K-AKT signaling. Major differences between LS and healthy controls were also noticed in pathways associated with cell cycle distribution, apoptosis, and autophagy. Our results highlight the key role of the GH-IGF1 axis in the initiation and progression of cancer. Furthermore, data are consistent with the concept that homozygous congenital IGF1 deficiency may confer protection against future tumor development.

Original languageEnglish
Pages (from-to)399-410
Number of pages12
JournalEndocrine-Related Cancer
Volume23
Issue number5
DOIs
StatePublished - May 2016

Keywords

  • Cancer protection
  • Dwarfism
  • Growth hormone receptor
  • Insulin-like growth factor-1
  • Laron syndrome

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