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Updated: Jul 17, 2026

Development and Application of Rapamycin-regulated Tyrosine Phosphatases
06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

RET/papillary thyroid carcinoma oncogenic signaling through the Rap1 small GTPase

Valentina De Falco1, Maria Domenica Castellone, Gabriella De Vita

  • 1Istituto di Endocrinologia ed Oncologia Sperimentale del CNR G. Salvatore, c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita' Federico II, via Sergio Pansini 5, 8-131 Naples, Italy.

Cancer Research
|January 11, 2007
PubMed

Insights

RET/papillary thyroid carcinoma (PTC) oncoproteins activate the Rap1 small GTPase, a key step in thyroid cancer progression. This activation influences cell proliferation and stress fiber formation, highlighting Rap1 as a potential therapeutic target.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Signaling

Background:

  • RET/papillary thyroid carcinoma (PTC) oncoproteins arise from RET receptor tyrosine kinase fusions.
  • Understanding the downstream signaling pathways of RET/PTC is crucial for thyroid cancer research.

Purpose of the Study:

  • To investigate the role of Rap1 small GTPase in RET/PTC1-mediated signaling.
  • To identify the molecular components involved in RET/PTC1-induced Rap1 activation.

Main Methods:

  • Utilized dominant-negative and small interfering RNA (siRNA) oligonucleotides.
  • Analyzed protein complex recruitment and kinase activation (BRAF, p42/p44 MAPK).
  • Assessed cell proliferation and stress fiber formation in thyroid follicular cells.

Main Results:

  • RET/PTC1 activates Rap1, dependent on RET Tyr(1062) phosphorylation.
  • RET/PTC1 recruits a complex including Gab1, CrkII, and C3G, essential for Rap1 activation.
  • Rap1 activation mediates RET/PTC1-induced BRAF and MAPK signaling, promoting cell proliferation.

Conclusions:

  • Rap1 is a downstream effector of RET/PTC oncoproteins.
  • Rap1 signaling contributes to the transformed phenotype of RET/PTC-expressing thyrocytes.
  • Targeting Rap1 may offer a therapeutic strategy for papillary thyroid carcinoma.

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