Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer cells exhibit accelerated rates of metabolism favoring glucose over fatty acid (FA) utilization. For both energy substrates, protein-mediated transport plays an essential role in facilitating glucose or FA movement across plasma membrane into the cells. Scarce data exist regarding the expression of glucose and/or FA transporter in cancer tissue. Therefore, we examined glucose (GLUT-1, GLUT-3, GLUT-4) and FA (FAT/CD36, FABPpm, FATP-1) transporter expressions at the protein and post-transcript (mRNA) levels in 35 endometrial carcinomas (G1, type endometrioid, FIGO I) and compared them with normal endometrial mucosa (n=10). Endometrial cancer tissue had significantly greater protein expression of GLUT-1, GLUT-3, and GLUT-4 (+ 40%; + 20%; + 24%; p<0.05, respectively) and, conversely, lower fatty acid (FAT/CD36 and FATP-1) transporter expression ( - 25%; p<0.05 and - 15%, p>0.05 respectively). Interestingly, mRNA content closely mirrors the changes, but only for glucose transporters and not fatty acid transporters. These results suggest the presence of metabolic switch of energy utilization in endometrial cancers favoring glucose consumption as the major source of energy.
 ...
PMID:Reversed glucose and fatty acids transporter expression in human endometrial cancer. 2235 75

Recent studies have identified FAT tumour suppressor homologue 4 (FAT4), an essential component of adherents junctions, involved in several cancers. However, its role in endometrial cancer (EC) remains unclear. In this study, we first analyzed the association between FAT4 expression and tumour stage, tumour type, and patient prognosis in 552 tumour samples and 35 non-tumour samples from The Cancer Genome Atlas (TCGA) database. The association of decreased FAT4 expression with advanced signature (lymph node metastasis, lymphovascular invasion and muscular infiltration) in EC patients was also confirmed by our own dataset. Stable FAT4 Knockdown promoted EC cell lines proliferation and invasion. FAT4 overexpression inhibited the parental cell phenotype. FAT4 silencing resulted in decreased phosphorylation of the LATS1/2 and YAP while increased YAP nuclear translocation which was associated with the promotion of proliferation and invasion. PCR array analysis of the negative control and shFAT4 HEC-1B cell lines revealed that the deubiquitinating enzyme USP51 was a FAT4 interacting target gene. Ablating USP51 by shRNA decreased cellular FAT4 protein level while overexpression of USP51 increased FAT4 protein level. Coimmunoprecipitation confirmed the direct binding of FAT4 and USP51 which was essential for FAT4's function in EC. The growth inhibitory effect of FAT4 was also attenuated by USP51 down-regulation. In conclusion, suppression of FAT4 by inactivation of deubiquitinating enzyme USP51 promoted proliferation and invasion of EC cells via inhibiting Hippo pathway.
 ...
PMID:FAT4-USP51 complex regulates the proliferation and invasion of endometrial cancer via Hippo pathway. 3121 54