细胞内视黄醇结合蛋白1（CRABP1）参与调节视黄醇信号通路。以往的研究对于CRABP1在肿瘤生物学中的作用给出了相互矛盾的结果，包括在不同类型的癌症中既有促肿瘤效应又有抑肿瘤效应。我们的生物信息学分析表明，在甲状腺癌中CRABP1的表达被下调。在甲状腺癌细胞中外源性表达CRABP1抑制了迁移和侵袭活性，但对细胞生长或细胞周期分布无影响。在转化的正常甲状腺滤泡上皮细胞中，CRABP1表达沉默增加了侵袭性。此外，CRABP1过表达与间质型表型下调相关。激酶磷酸化谱分析表明，CRABP1过表达伴随着表皮生长因子（EGF）受体磷酸化及其下游Akt、STAT3和FAK磷酸化水平的下降，而外源性EGF处理能够逆转这种现象。我们的组织微阵列免疫组化分析显示，CRABP1表达与分化型甲状腺癌的疾病分期呈负相关。综上所述，我们的研究结果表明，在甲状腺癌中CRABP1的表达被异常降低，并且这种下调通过调节EGF受体信号通路至少在一定程度上促进了上皮-间质转化。 © 2023 Wiley Periodicals LLC.

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.© 2023 Wiley Periodicals LLC.