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AMFR

autocrine motility factor receptor, E3 ubiquitin protein ligase;AMFR;autocrine motility factor receptor, E3 ubiquitin protein ligase

E3 ubiquitin-protein ligase AMFR|RING finger protein 45

16q21

protein-coding

AMFR, autocrine motility factor receptor, also called gp78, is a cell surface cytokine receptor which has a dual role as an E3 ubiquitin ligase in endoplasmic reticulum-associated degradation. AMFR expression is associated with tumor malignancy. We here investigated the clinical significance of AMFR and its role in metastasis and prognosis in gastric cancer. expression of AMFR, E-cadherin and N-cadherin in cancer tissues and matched adjacent normal tissues from 122 gastric cancer (GC) patients undergoing surgical resection was assessed by immunohistochemistry. Levels of these molecules in 17 cases selected randomly were also analysed by Western blotting. AMFR expression was significantly increased in gastric cancer tissues, and associated with invasion depth and lymph node metastasis. Kaplan-Meier analysis showed AMFR expression correlated with poor overall survival and an increased risk of recurrence in the GC cases. Cox regression analysis suggested AMFR to be an independent predictor for overall and recurrence-free survival. E-cadherin expression was decreased in gastric cancer tissues; conversely, N-cadherin was increased. expression of AMFR negatively correlated with E-cadherin expression, whereas N-cadherin expression showed a significant positive correlation with AMFR expression. AMFR might be involved in the regulation of epithelial-mesenchymal transition, with aberrant expression correlating with a poor prognosis and promoting invasion and metastasis in GCs.

Our previous study identified RhoC as an invasion and metastasis marker in hepatocellular carcinoma patients. Recent document suggested RhoGTPase is required for autocrine motility factor signaling. In this study, we questioned whether there is a correlation between expression of autocrine motility factor receptor and RhoC. Furthermore, we questioned whether elevated expression of autocrine motility factor correlates with metastasis and poor prognosis of HCC. The mRNA expression level of AMFR and RhoC were examined by RT-PCR in 25 cases of HCC and pericarcinomatous liver tissues (PCLT). In addition, the correlation between the expression level of AMFR and clinical pathologic parameters was analyzed. Furthermore, follow-up information was collected to evaluate the prognostic value of AMFR for HCC patients. Our results showed that the expression of AMFR and RhoC significantly increased in HCC compared with PCLT; extrahepatic metastatic lesions expressed significantly higher levels of AMFR and RhoC than corresponding intrahepatic HCC tissues. There is a highly significant correlation of AMFR expression levels with tumor vein invasion, number of tumor nodes, and tumor stage. Anticipatively, positive correlation was observed between mRNA expression of AMFR and RhoC gene. Furthermore, the HCC patients with high-expression of AMFR had significant high recurrence/metastasis and shorter survival than those with low-expression of AMFR. Together, our findings suggested a strong correlation between the expression of AMFR and RhoC and also a correlation between overexpression of them and invasion and metastasis of HCC. Furthermore, our data indicated AMFR as a potential prognosis for HCC.

metastasis is the primary cause of mortality from cancer, but the mechanisms leading to metastasis are poorly understood. In particular, relatively little is known about metastasis in cancers of mesenchymal origins, which are known as sarcomas. Approximately ten proteins have been characterized as 'metastasis suppressors', but how these proteins function and are regulated is, in general, not well understood. Gp78 (also known as AMFR or RNF45) is a RING finger E3 ubiquitin ligase that is integral to the endoplasmic reticulum (ER) and involved in ER-associated degradation (ERAD) of diverse substrates. Here we report that expression of gp78 has a causal role in the metastasis of an aggressive human sarcoma and that this prometastatic activity requires the E3 activity of gp78. Further, gp78 associates with and targets the transmembrane metastasis suppressor, KAI1 (also known as CD82), for degradation. Suppression of gp78 increases KAI1 abundance and reduces the metastatic potential of tumor cells, an effect that is largely blocked by concomitant suppression of KAI1. An inverse relationship between these proteins was confirmed in a human sarcoma tissue microarray. Whereas most previous efforts have focused on genetic mechanisms for the loss of metastasis suppressor genes, our results provide new evidence for post-translational downregulation of a metastasis suppressor by its ubiquitin ligase, resulting in abrogation of its metastasis-suppressing effects.