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CRIM1

Cysteine-rich motor neuron1 protein (CRIM1), a novel antagonist of bone morphogenetic proteins (BMPs), is reported to regulate the processing of BMPs preprotein into mature protein and the delivery of BMPs to the cell surface. Previous studies have shown that CRIM1 is an important player in regulating placental development, organogenesis, angiogenesis and kidney disease. Here, we propose that CRIM1 is a potential risk factor in cancer progression and metastasis. The epithelial-mesenchymal transition (EMT), which is characterized by the loss of epithelial phenotype and the acquisition of mesenchymal characteristics, is closely associated with invasion and metastasis of tumors. At the same time, it is hard for us to ignore the importance of angiogenesis in the genesis and progression of cancer. In this review we summarized the construction and previous researches of CRIM1. Furthermore, as it may be involved in tumor development and progression through its potential role in the EMT, capillary formation and angiogenesis maintenance, we proposed for the first time that CRIM1 may be a cancer related factor.

CRIM1 is a membrane protein that has been reported to be related to cell proliferation. CRIM1 is expressed in renal carcinoma cells, but its involvement in proliferation and malignant transformation remains unclear. We analyzed whether alterations in the characteristics of cancer cells are observed following knockdown of CRIM1. Decreased expression of CRIM1 did not affect proliferation or anchorage-independent growth. The results of wound healing and invasion assays showed that reduced expression of CRIM1 increased cells' migratory and invasive abilities. expression analysis of factors involved in migration and invasion in CRIM1-knockdown cells revealed that expression of the cell adhesion factor E-cadherin declined and expression of claudin-1, which is upregulated in metastatic cancer cells, increased. In addition, increased expression of matrix metalloproteinase (MMP) 2 and MMP9, protease essential for cancer cell invasiveness, was observed. Furthermore, an increase in phosphorylated focal adhesion kinase (FAK), which increases cell migration, was observed. Increased expression of the E-cadherin transcription repressors Snail, Slug, and ZEB-1 were observed, and mRNA levels of E-cadherin were decreased. Therefore, expression of E-cadherin is thought to be decreased by both suppression of E-cadherin mRNA expression and promotion of degradation of the E-cadherin protein. In addition, expression of CRIM1 was decreased in renal cancer cells undergoing epithelial-mesenchymal transition (EMT) stimulated by tumor necrosis factor alpha (TNF-alpha). Thus, CRIM1 regulates the expression of several EMT-related factors and appears to play a role in suppressing migration and invasion through control of EMT.