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)

During the last two decades, a group of homeobox-containing genes, the HOX gene family, has been studied both in the context of embryonic development and neoplasia. In particular, there is accumulating evidence of the involvement of HOX abnormalities in a variety of malignancies, including breast cancer. However, little is known about the association of HOX genes with endometrial cancer, which is the most common malignancy of the female genital tract and is thought to be dependent on estrogen, like breast cancer. In this study, we detected overexpression of the HOXB13 gene in endometrial cancer cells and tissues from patients by quantitative real-time RT-PCR. To investigate whether overexpression of HOXB13 is involved in invasion or metastasis of endometrial cancer, we transfected antisense HOXB13/pcDNA3.1+ plasmid vector into endometrial cancer AN3CA cells by electroporation and performed in vitro chemoinvasion assay. We revealed that the invasive ability of antisense-transfectants showed a 90% reduction compared with parental cells and control transfectants (p<0.01). In addition, administration of 17beta-estradiol induced time- and dose-dependent responses of the HOXB13 expression in endometrial cancer AN3CA cells. These results suggest that overexpression of HOXB13 in endometrial cancer may be associated with the invasive ability of cancer cells with regulation by estrogen.
 ...
PMID:Regulation of tumor invasion by HOXB13 gene overexpressed in human endometrial cancer. 1575 48

Although many studies have confirmed the relationship between obesity and endometrial cancer (EC), the molecular mechanism between obesity and EC progression has not been elucidated. Overexpression of fat mass and the obesity associated protein FTO leads to weight gain, although recently it has been discovered that FTO can serve as a demethylase which erases N6-methyladenosine (m6A) modification and regulates the metabolization of mRNAs. In this study, we found high expression of FTO in metastatic EC and that this action promote both metastasis and invasion in vivo and in vitro. Mechanistically, FTO can catalyse demethylation modification in 3'UTR region of HOXB13 mRNA, thereby abolishing m6A modification recognition with the YTHDF2 protein. Decreasing HOXB13 mRNA decay and increasing HOXB13 protein expression was accompanied by WNT signalling pathway activation and the expression of downstream proteins, leading to tumour metastasis and invasion. We also found the WNT signalling pathway inhibitor ICG-001 can block HOXB13 gene-induced tumour metastasis, therefore ICG-001 may be a promising molecular intervention. This study provides insight into the relationship between obesity and the pathogenesis of endometrial cancer while highlighting future areas of research.
 ...
PMID:FTO demethylates m6A modifications in HOXB13 mRNA and promotes endometrial cancer metastasis by activating the WNT signalling pathway. 3310 87