Ret regulates human medullary thyroid cancer cell proliferation through cdk5 and stat3 activation

Chia Herng Yue, Muhammet Oner, Chih Yuan Chiu, Mei Chih Chen, Chieh Lin Teng, Hsin Yi Wang, Jer Tsong Hsieh, Chih Ho Lai, Ho Lin

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Medullary thyroid cancer (MTC) is a neuroendocrine tumor that arises from the parafollicular C-cells, which produces the hormone calcitonin. RET is a transmembrane receptor proteintyrosine kinase, which is highly expressed in MTC. Our previous studies reported that cyclin-dependent kinase 5 (CDK5) plays a crucial role in cancer progression, including MTC. However, the role of CDK5 in GDNF-induced RET signaling in medullary thyroid cancer proliferation remains unknown. Here, we investigated RET activation and its biochemically interaction with CDK5 in GDNF-induced medullary thyroid cancer proliferation. Our results demonstrated that GDNF stimulated RET phosphorylation and thus subsequently resulted in CDK5 activation by its phosphorylation. Activated CDK5 further caused STAT3 activation by its specific phosphorylation at Ser727. Moreover, we also found that GDNF treatment enhanced ERK1/2 and EGR1 activity, which is involved in p35 activation. Interestingly, we identified for the first time that CDK5 physically interacted with RET protein in MTC. Overall, our results provide a new mechanism for medullary thyroid cancer cell proliferation, suggesting that targeting CDK5 may be a promising therapeutic candidate for human medullary thyroid cancer in the near future.

Original languageEnglish (US)
Article number860
Issue number6
StatePublished - Jun 2021


  • CDK5/p35
  • EGR1
  • ERK1/2
  • Human medullary thyroid carcinoma
  • RET
  • STAT3

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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