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RET receptor signaling: Function in development, metabolic disease, and cancer

Masahide Takahashi1,2

  • 1International Center for Cell and Gene Therapy, Fujita Health University.

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
|March 14, 2022
PubMed

Insights

The RET proto-oncogene is vital for development and linked to cancers. Its signaling pathways, activated by GDNF and GDF15, offer new therapeutic targets for RET-altered cancers and metabolic diseases.

Area of Science:

  • Molecular Biology
  • Oncology
  • Developmental Biology

Background:

  • The RET proto-oncogene encodes a receptor tyrosine kinase implicated in various cancers and developmental disorders.
  • RET signaling is physiologically activated by glial cell line-derived neurotrophic factor (GDNF) family ligands and coreceptors (GFRα).
  • Dysregulation of RET signaling contributes to conditions like thyroid cancer, lung cancer, multiple endocrine neoplasia, and Hirschsprung's disease.

Purpose of the Study:

  • To review the diverse roles of RET signaling in biological development.
  • To explore the involvement of RET in metabolic regulation, including body weight control via GDF15.
  • To highlight the therapeutic potential of targeting RET in cancer treatment.

Main Methods:

  • Literature review of studies on RET proto-oncogene function.
  • Analysis of RET signaling pathways involving GDNF and GDF15.
  • Examination of clinical data on RET-altered cancers and therapeutic interventions.

Main Results:

  • RET signaling is essential for the development of the enteric nervous system, kidneys, and reproductive cells.
  • Growth differentiation factor-15 (GDF15) activates RET, influencing metabolism and anorexia-cachexia syndrome.
  • RET-specific kinase inhibitors have shown significant promise in treating RET-altered cancers.

Conclusions:

  • RET plays a multifaceted role in development, metabolic homeostasis, and oncogenesis.
  • Understanding RET signaling pathways provides insights into treating developmental disorders and metabolic diseases.
  • Targeted therapies against RET offer a promising avenue for managing various RET-driven malignancies.
Keywords:
GDNF family ligandsHirschsprung’s diseaseRET protooncogenebody weight controlcancerkidney development

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