| Gene information | Literature | Expression | lncRNA | Mutation | Homolog |
Basic Information | |
|---|---|
Gene ID | 57154 |
Name | SMURF1 |
Synonymous | SMAD specific E3 ubiquitin protein ligase 1;SMURF1;SMAD specific E3 ubiquitin protein ligase 1 |
Definition | E3 ubiquitin ligase SMURF1|E3 ubiquitin-protein ligase SMURF1|SMAD-specific E3 ubiquitin-protein ligase 1|Smad ubiquitination regulatory factor 1|Smad-specific E3 ubiquitin ligase 1|hSMURF1 |
Position | 7q22.1 |
Gene type | protein-coding |
Title | Abstract |
| SMURF1 amplification promotes invasiveness in pancreatic cancer. | Pancreatic cancer is a deadly disease, and new therapeutic targets are urgently needed. We previously identified DNA amplification at 7q21-q22 in pancreatic cancer cell lines. Now, by high-resolution genomic profiling of human pancreatic cancer cell lines and human tumors (engrafted in immunodeficient mice to enrich the cancer epithelial fraction), we define a 325 Kb minimal amplicon spanning SMURF1, an E3 ubiquitin ligase and known negative regulator of transforming growth factor beta (TGFbeta) growth inhibitory signaling. SMURF1 amplification was confirmed in primary human pancreatic cancers by fluorescence in situ hybridization (FISH), where 4 of 95 cases (4.2%) exhibited amplification. By RNA interference (RNAi), knockdown of SMURF1 in a human pancreatic cancer line with focal amplification (AsPC-1) did not alter cell growth, but led to reduced cell invasion and anchorage-independent growth. Interestingly, this effect was not mediated through altered TGFbeta signaling, assayed by transcriptional reporter. Finally, overexpression of SMURF1 (but not a catalytic mutant) led to loss of contact inhibition in NIH-3T3 mouse embryo fibroblast cells. Together, these findings identify SMURF1 as an amplified oncogene driving multiple tumorigenic phenotypes in pancreatic cancer, and provide a new druggable target for molecularly directed therapy. |
| CKIP-1 acts as a colonic tumor suppressor by repressing oncogenic Smurf1 synthesis and promoting Smurf1 autodegradation. | Dysregulation of cellular signaling pathways can lead to colon cancer. However, research on the key signaling effectors or regulators in colon carcinogenesis is limited. Casein kinase-2 interacting protein-1 (CKIP-1; also known as PLEKHO1) is crucial during adult bone formation and is a promising drug target for osteoporosis therapy. In this study, we observed that CKIP-1 was downregulated in human colon cancer tissues and colon cancer cell lines, and this result was correlated with colon cancer progression. CKIP-1 silencing in colon cancers involved promoter methylation. In colon cancer HCT116 and SW480 cells, CKIP-1 overexpression inhibited cell growth and migration. CKIP-1 also suppressed in-vivo tumor formation. Notably, the growth-suppressive role of CKIP-1 was dependent on the downregulation of the cell cycle-regulated oncogene Smad ubiquitylation regulatory factor-1 (Smurf1). During cell cycle progression, phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling increased Smurf1 production by an mTOR-dependent translational control mechanism. Rapamycin, the mTOR inhibitor, significantly reduced Smurf1 protein levels, and Smurf1 was degraded in mitosis. In colon cancer, CKIP-1 controlled Smurf1 expression by suppressing PI3K/Akt/mTOR signaling and enhancing Smurf1 autodegradation, and CKIP-1 downregulation was correlated with Smurf1 upregulation in colon carcinogenesis. These findings provide novel insight into the mechanisms of the candidate tumor suppressor CKIP-1. |