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RCAN1-4 is a thyroid cancer growth and metastasis suppressor

Chaojie Wang1,2, Motoyasu Saji1, Steven E Justiniano1

  • 1Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine.

JCI Insight
|March 15, 2017
PubMed

Insights

Regulator of calcineurin 1, isoform 4 (RCAN1-4) suppresses thyroid cancer growth and metastasis. Loss of RCAN1-4 promotes tumor progression and lung metastasis, partly via nuclear factor, erythroid 2-like 3 (NFE2L3).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Metastasis suppressors are crucial for controlling tumor progression.
  • Loss of these suppressors correlates with aggressive cancer phenotypes.
  • Regulator of calcineurin 1, isoform 4 (RCAN1-4) was previously identified as a potential metastasis suppressor.

Purpose of the Study:

  • To investigate the in vivo role of endogenous RCAN1-4 in thyroid cancer.
  • To identify downstream effectors of RCAN1-4 in cancer progression.
  • To evaluate RCAN1-4 as a therapeutic target for thyroid cancer.

Main Methods:

  • Development of RCAN1-4 knockdown stable thyroid cancer cells.
  • Subcutaneous and intravenous xenograft metastasis models in vivo.
  • Microarray analysis to identify downstream targets.
  • Analysis of human thyroid cancer samples (TCGA).

Main Results:

  • RCAN1-4 knockdown significantly promoted thyroid tumor growth and lung metastasis in vivo.
  • Stable induction of RCAN1-4 expression inhibited thyroid cancer cell growth and invasion.
  • Nuclear factor, erythroid 2-like 3 (NFE2L3) was identified as a key downstream mediator.
  • NFE2L3 overexpression was observed in human thyroid tumors and distant metastases.

Conclusions:

  • RCAN1-4 acts as a critical suppressor of thyroid cancer growth and metastasis in vivo.
  • The tumor-promoting effects of RCAN1-4 loss are mediated, in part, by NFE2L3.
  • RCAN1-4 represents a potential therapeutic target for inhibiting thyroid cancer progression.

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