Endometrial cancer is one of the most common gynecological malignancies affecting post-menopausal women, yet the underlying mechanisms are not well understood. Dystroglycan (DG) is a large glycoprotein, consisting of α- and β-subunits that are non-covalently associated with each other. Modifications to α-DG have been linked to a variety of cancers, where the N-terminus of α-DG (α-DG-N) is post-translationally removed by a furin-like enzyme. However, the functional significance of α-DG-N removal is unknown. Our previous studies have established that the α-DG cleavage enzyme furin is significantly up-regulated in endometrial cancer. This study aimed to investigate the importance of α-DG-N removal in post-menopausal endometrial cancer. We demonstrated that α-DG-N removal predominantly occurred in early stage endometrial cancer tissues, and that the cleaved α-DG-N was significantly elevated in the uterine lavage of early grade endometrial cancer patients. Furthermore, α-DG-N removal significantly decreased the tight junction integrity and polarity of the endometrial epithelial cells, promoting the loss of polarity markers scribble and atypical protein kinase C (aPKC) and reducing the trans-epithelial electrical resistance. The removal of α-DG-N also sensitized the cells for estrogen-dependent proliferation. These results strongly suggest that α-DG-N removal plays an important role in early stage development of endometrial cancer, and that the elevated levels of α-DG-N in uterine fluid may provide a biomarker for early detection of endometrial cancer.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669861 | PMC |
| http://dx.doi.org/10.18632/oncotarget.17286 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Lymph node assessment at the time of robotic hysterectomy for endometrial intraepithelial neoplasia: A cost-effectiveness analysis.
Gynecol Oncol
January 2025
Division of Gynecologic Oncology, St. Luke's University Health Network, Bethlehem, PA, United States of America.
Objective: We sought to determine the cost-effectiveness (CE) of lymph node dissection (LND) at the time of hysterectomy for endometrial intraepithelial neoplasia (EIN).
Methods: A decision analytic model was created to evaluate the strategies of routine full LND, sentinel lymph node dissection (SNLD), SNLD without advancing to full LND in the event of non-mapping, and full LND based on Mayo Criteria, versus no LND. Patients in the no LND group and those in the SLND group without advancement to full LND in the event of non-mapping who were found to have EC on final pathology and suspicious post-operative imaging underwent full LND.
Added prognostic value of sentinel lymph node mapping in endometrial cancer to molecular subgroups.
Gynecol Oncol
January 2025
Department of Obstetrics and Gynecology, Bern University Hospital and University of Bern, Bern, Switzerland.
Objective: Treatment approaches for endometrial cancer became more personalized in the last decade, mainly due to two key advancements - sentinel lymph node (SLN) mapping and molecular classification. However, their prognostic interaction remains relatively unexplored.
Methods: This retrospective cohort study included patients with endometrial cancer, who underwent surgical treatment including SLN mapping at the Bern University Hospital, Switzerland.
Elevated LINC00115 expression correlates with aggressive endometrial cancer phenotypes via JAK/STAT pathway modulation.
Hum Mol Genet
January 2025
Department of Reproductive Medicine, The First Affiliated Hospital of Henan University of CM, No. 19, Renmin Road, Jinshui District, Zhengzhou City, Henan Province, China.
This study systematically explores the oncogenic role of the long non-coding RNA (lncRNA) LINC00115 in endometrial cancer (EC) and reveals its unique mechanism in promoting proliferation, invasion, and metastasis via the JAK/STAT signaling pathway. LINC00115 is significantly upregulated in EC tissues and closely associated with advanced TNM staging and lymph node metastasis. Functional assays showed that knockdown of LINC00115 suppressed EC cell proliferation, invasion, and metastasis, while overexpression enhanced these malignant behaviors.
View Article and Find Full Text PDFArticle Synopsis
- PAX2 is identified as an endometrial tumor suppressor frequently inactivated through a unique epigenetic mechanism, rather than promoter hypermethylation.
- In 80% of endometrial cancers, the loss of PAX2 is linked to transcriptional silencing, which alters chromatin features, contributing to cancer development.
- The research highlights new pathways for understanding endometrial cancer origins, potentially influencing future diagnosis and treatment approaches.
A case of large uterine cystic adenomyosis outside the uterus after laparoscopic myomectomy: a case report and literature review.
BMC Womens Health
January 2025
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No.36 Sanhao Street, Heping District, Shenyang, Liaoning Province, 110004, China.
Background: Uterine cystic adenomyosis is a rare form of focal adenomyosis that is primarily located within the myometrium. In this case report, we present a unique case of adult uterine cystic adenomyosis found outside the uterus following laparoscopic myomectomy.
Case Presentation: The patient was a 36-year-old Chinese woman who had previously undergone laparoscopic surgery at our hospital to remove a 4 cm diameter diameter uterine fibroid six years prior.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!