Downregulation of cellular retinoic acid binding protein 1 fosters epithelial–mesenchymal transition in thyroid cancer

Yi Chiung Hsu, Wen Chien Huang, Chi Yu Kuo, Ying Syuan Li, Shih Ping Cheng

Research output: Contribution to journalArticlepeer-review

Abstract

Cellular retinoic acid binding protein 1 (CRABP1) participates in the regulation of retinoid signaling. Previous studies showed conflicting results regarding the role of CRABP1 in tumor biology, including protumorigenic and tumor-suppressive effects in different types of cancer. Our bioinformatics analyses suggested that CRABP1 expression was downregulated in thyroid cancer. Ectopic expression of CRABP1 in thyroid cancer cells suppressed migratory and invasive activity without affecting cell growth or cell cycle distribution. In transformed normal thyroid follicular epithelial cells, silencing of CRABP1 expression increased invasiveness. Additionally, CRABP1 overexpression was associated with downregulation of the mesenchymal phenotype. Kinase phosphorylation profiling indicated that CRABP1 overexpression was accompanied by a decrease in phosphorylation of epidermal growth factor (EGF) receptor and downstream phosphorylation of Akt, STAT3, and FAK, which were reversed by exogenous EGF treatment. Immunohistochemical analysis of our tissue microarrays revealed an inverse association between CRABP1 expression and disease stage of differentiated thyroid cancer. Taken together, our results suggest that CRABP1 expression is aberrantly lost in thyroid cancer, and this downregulation promotes the epithelial–mesenchymal transition at least partly through modulating EGF receptor signaling.

Original languageEnglish
Pages (from-to)1935-1946
Number of pages12
JournalMolecular Carcinogenesis
Volume62
Issue number12
DOIs
StatePublished - Dec 2023

Keywords

  • CRABP1
  • epidermal growth factor signaling
  • epithelial–mesenchymal transition
  • thyroid cancer

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