Cellular Retinoic Acid Binding Protein 2 Is Strikingly Downregulated in Human Esophageal Squamous Cell Carcinoma and Functions as a Tumor Suppressor.
Cellular Retinoic Acid Binding Protein 2 Is Strikingly Downregulated in Human Esophageal Squamous Cell Carcinoma and Functions as a Tumor Suppressor.
复制标题
细胞视黄酸结合蛋白 2 在人食管鳞状细胞癌中显着下调并发挥肿瘤抑制作用
DOI：
10.1371/journal.pone.0148381
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Pan Q
中科院分区：
文献类型：
--
作者：
Yang Q;Wang R;Xiao W;Sun F;Yuan H;Pan Q
食管鳞癌是中国特别是河南省食管癌的主要病理类型，预后差，5年生存率低。细胞维甲酸结合蛋白2(CRABP2)是维甲酸(RA)和脂钙蛋白/胞质脂肪酸结合蛋白家族的成员，通过视黄酸受体(RAR)和PPARβ/Delta受体在肿瘤发生中发挥完全相反的作用。目前，CRABP2在食管癌发生发展中的生物学作用尚未见报道。在此，我们首先检测了CRABP2在mRNA和蛋白水平的表达，发现CRABP2在临床ESCC组织中表达显著下调，并与肿瘤的发生部位、病理类型、TNM分期、肿瘤大小、浸润深度和细胞分化程度密切相关。此外，生物学功能检测表明，CRABP2在体内外均能显著抑制细胞生长、诱导细胞凋亡、阻断细胞转移，从而在食管鳞癌的发生发展过程中发挥肿瘤抑制作用。总之，我们的发现简化了CRABP2可能是诊断和预测ESCC发展的一个有效的分子标志物。
Esophageal squamous cell carcinoma (ESCC) is the predominant pathotype of esophageal carcinoma (EC) in China, especially in Henan province, with poor prognosis and limited 5-year survival rate. Cellular retinoic acid binding protein 2 (CRABP2) is a member of the retinoic acid (RA) and lipocalin/cytosolic fatty-acid binding protein family and plays a completely contrary role in tumorigenesis through the retinoid signaling pathway, depending on the nuclear RA receptors (RAR) and PPARbeta/delta receptors. Presently, the biological role of CRABP2 in the development of ESCC has never been reported. Here, we firstly evaluated the expression of CRABP2 at both mRNA and protein levels and showed that it was remarkably downregulated in clinical ESCC tissues and closely correlated with the occurrence position, pathology, TNM stage, size, infiltration depth and cell differentiation of the tumor. Additionally, the biological function assays demonstrated that CRABP2 acted as a tumor suppressor in esophageal squamous carcinogenesis by significantly inhibiting cell growth, inducing cell apoptosis and blocking cell metastasis both in vitro and in vivo. All in all, our finding simplicate that CRABP2 is possibly an efficient molecular marker for diagnosing and predicting the development of ESCC.