CRABP1 provides high malignancy of transformed mesenchymal cells and contributes to the pathogenesis of mesenchymal and neuroendocrine tumors

Abstract

CRABP1 (cellular retinoic acid binding protein 1) belongs to the family of fatty acid binding proteins. Retinoic acid binding is the only known functional activity of this protein. The role of CRABP1 in human carcinogenesis remains poorly understood. Here, for the first time we demonstrated pro-metastatic and pro-tumorigenic activity of CRABP1 in mesenchymal tumors. Further functional analysis revealed that the pro-tumorigenic effect of CRABP1 does not depend on retinoic acid binding activity. These results suggest that CRABP1 could have an alternative intracellular functional activity that contributes to the high malignancy of transformed mesenchymal cells. Microarray analysis detected CRABP1-mediated alterations in the expression of about 100 genes, including those encoding key regulatory proteins. CRABP1 is ubiquitously expressed in monophasic synovial sarcomas, while in biphasic synovial sarcomas it is expressed uniquely by the spindle cells of the aggressive mesenchymal component. High level of CRABP1 expression is associated with lymph node metastasis and poor differentiation/high grade of pancreatic neuroendocrine tumors (pNETs). Presented data suggest CRABP1 as a promising biomarker of pNETs' clinical behavior. Our results give the first evidence of pro-tumorigenic and pro-metastatic activity of CRABP1 in mesenchymal and neuroendocrine tumors.

miR-93/miR-106b/miR-375-CIC-CRABP1: a novel regulatory axis in prostate cancer progression

“…The high throughput mRNA sequencing analysis revealed that a total of 262 genes (159 up-regulated, and 103 down-regulated) was differentially expressed (Fold change (log2) > 2 and P-value < 0.05) in the shCIC-3 PC-3 cells compared with control cells ( Supplementary Table 2 ). Among the differentially expressed genes, cellular retinoic acid binding protein 1 ( CRABP1 ) primarily caught our attention, because of the highest fold increase upon knock-down of CIC in PC-3 cells ( Supplementary Table 2 ) and its previously known pro-tumorigenic and pro-metastatic activity in mesenchymal tumors [ 18 ]. Moreover, it is known that CRABP1 is overexpressed in castration-resistant prostate cancer cells [ 19 ].…”

Gene Expression Signature Predictive of Neuroendocrine Transformation in Prostate Adenocarcinoma

“…SCG2 encodes for secretogranin, among the NE markers identified in prostate small cell carcinomas by a molecular characterization study that highlighted a diverse repertoire of genes reflecting characteristics of their NE cell of origin [45]. CRABP1 has a pro-tumorigenic and a pro-metastatic activity in mesenchymal and neuroendocrine tumors [46]. SLC35D3, which showed a dramatic up-regulation also in NEPC PDXs from the independent dataset GSE59984 (data not shown), is specifically expressed in the substantia nigra, striatum, and olfactory bulb in mouse brain and it functions as an ER chaperone for dopamine receptor D1 trafficking to the plasma membrane [47].…”

Gastric Damage and Cancer-Associated Biomarkers in Helicobacter pylori-Infected Children

“…CRABP1 (Cellular retinoic acid-binding protein 1) is responsible for binding retinoic acid transporting it into cells. Evidence for its role in carcinogenesis is controversial, showing both pro-apoptotic and pro-metastatic properties in vitro (Kainov et al, 2014;Persaud et al, 2016). Its hypermethylation and/or underexpression has been described in colorectal, breast, ovarian, esophageal and cervical cancers (Tanaka et al, 2007;Miyake et al, 2011;Liu et al, 2015;Arellano-Ortiz et al, 2016;Cha et al, 2016).…”