The significance of post-translational removal of α-DG-N in early stage endometrial cancer development

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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 posttranslationally 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.

Original languageEnglish
Pages (from-to)81942-81952
Number of pages11
JournalOncotarget
Volume8
Issue number47
DOIs
Publication statusPublished - 1 Jan 2017

Keywords

  • Cell polarity
  • Dystroglycan
  • Endometrial cancer
  • Estrogen
  • Tight junction

Cite this

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title = "The significance of post-translational removal of α-DG-N in early stage endometrial cancer development",
abstract = "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 posttranslationally 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.",
keywords = "Cell polarity, Dystroglycan, Endometrial cancer, Estrogen, Tight junction",
author = "Sophea Heng and Jemma Evans and Salamonsen, {Lois A.} and Jobling, {Tom W.} and Guiying Nie",
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The significance of post-translational removal of α-DG-N in early stage endometrial cancer development. / Heng, Sophea; Evans, Jemma; Salamonsen, Lois A.; Jobling, Tom W.; Nie, Guiying.

In: Oncotarget, Vol. 8, No. 47, 01.01.2017, p. 81942-81952.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

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AU - Evans, Jemma

AU - Salamonsen, Lois A.

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AU - Nie, Guiying

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Y1 - 2017/1/1

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