Morphological Changes, Cadherin Switching, and Growth Suppression in Pancreatic Cancer by GALNT6 Knockdown

Tarhan, Yunus Emre; Kato, Taigo; Jang, Miran; Haga, Yoshimi; Ueda, Koji; Nakamura, Yusuke; Park, Jae-Hyun

doi:10.1016/j.neo.2016.03.005

Cited by 32 publications

(49 citation statements)

References 22 publications

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“…Knockdown of GalNAc-T6 was recently shown to induce a switch from P-cadherin to E-cadherin expression in pancreatic cancer cells (67). However, our colon transcriptome data indicated rather an opposite shift from E-cadherin to P-cadherin expression (Fig.…”

Section: Cancer-associated Expression Of Human Pp-galnac-t6mentioning

confidence: 54%

Section: Cancer-associated Expression Of Human Pp-galnac-t6mentioning

confidence: 99%

“…In breast cancer, overexpression of GalNAc-T6 was reported to decrease cellular adhesion and disrupt mammary acinar morphogenesis (66,67,82). Furthermore, it has been shown that GalNAc-T6 expression in pancreatic cancer causes a switch from E-cadherin expression to P-cadherin expression affecting cellular adhesion to the underlying matrix (67). The cancer-associated expression of GalNAc-T6 has also been proposed to induce EMT (66,68,83) as evidenced by decreased E-cadherin expression and enhanced expression of mesenchymal markers (68).…”

Section: Cancer-associated Expression Of Human Pp-galnac-t6mentioning

confidence: 99%

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De novo expression of human polypeptide N-acetylgalactosaminyltransferase 6 (GalNAc-T6) in colon adenocarcinoma inhibits the differentiation of colonic epithelium

Lavrsen

Dabelsteen

Vakhrushev

et al. 2018

Journal of Biological Chemistry

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Edited by Eric R. FearonAberrant expression of O-glycans is a hallmark of epithelial cancers. Mucin-type O-glycosylation is initiated by a large family of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) that target different proteins and are differentially expressed in cells and organs. Here, we investigated the expression patterns of all of the GalNAc-Ts in colon cancer by analyzing transcriptomic data. We found that GalNAc-T6 was highly up-regulated in colon adenocarcinomas but absent in normal-appearing adjacent colon tissue. These results were verified by immunohistochemistry, suggesting that GalNAc-T6 plays a role in colon carcinogenesis. To investigate the function of GalNAc-T6 in colon cancer, we used precise gene targeting to produce isogenic colon cancer cell lines with a knockout/rescue system for GALNT6. GalNAc-T6 expression was associated with a cancer-like, dysplastic growth pattern, whereas GALNT6 knockout cells showed a more normal differentiation pattern, reduced proliferation, normalized cell-cell adhesion, and formation of crypts in tissue cultures. O-Glycoproteomic analysis of the engineered cell lines identified a small set of GalNAc-T6 -specific targets, suggesting that this isoform has unique cellular functions. In support of this notion, the genetically and functionally closely related GalNAc-T3 homolog did not show compensatory functionality for effects observed for GalNAc-T6. Taken together, these data strongly suggest that aberrant GalNAc-T6 expression and site-specific glycosylation is involved in oncogenic transformation.

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Section: Cancer-associated Expression Of Human Pp-galnac-t6mentioning

confidence: 54%

Section: Cancer-associated Expression Of Human Pp-galnac-t6mentioning

confidence: 99%

Section: Cancer-associated Expression Of Human Pp-galnac-t6mentioning

confidence: 99%

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De novo expression of human polypeptide N-acetylgalactosaminyltransferase 6 (GalNAc-T6) in colon adenocarcinoma inhibits the differentiation of colonic epithelium

Lavrsen

Dabelsteen

Vakhrushev

et al. 2018

Journal of Biological Chemistry

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“…It has been shown to be upregulated when cells are differentiating, and in malignancy [21][22][23][24]. Expression is minimal in normal tissues [21].…”

Section: Molecular Geneticsmentioning

confidence: 99%

“…pp-GalNAc-T6 has also been studied once in pancreatic cancer [23,55]. pp-GalNAc-T6 expression is rare in normal ductal epithelium of the pancreas.…”

Section: Role In Cancermentioning

confidence: 99%

UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase- 6 (pp-GalNAc-T6): Role in Cancer and Prospects as a Drug Target

Banford¹,

Timson

2016

CCDT

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UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyl transferase-6 (pp-GalNAc-T6) is a member of the N-acetyl-D-galactosamine transferase family. It catalyzes the addition of N-acetyl-D-galactosamine to proteins, often the first step in Oglycosylation of proteins. Glycosylated proteins play important roles in vivo in the cell membrane. These are often involved in cell-cell adhesion, cytoskeleton regulation and immune recognition. pp-GalNAc-T6 has been shown to be upregulated in a number of types of cancer. Abnormally glycosylated forms of mucin 1 (substrate of the enzyme), are used clinically as a biomarker for breast cancer. There is potential for other products of the pp-GalNAc-T6 catalyzed reaction to be used. It is also possible that pp-GalNAc-T6 itself could be used as a biomarker, since levels of this protein tend to be low in nonmalignant tissues. pp-GalNAc-T6 has been implicated in malignant transformation and metastasis of cancer cells. As such, it has considerable potential as a target for chemotherapy. To date, no selective inhibitors of the enzyme have been identified. However, general inhibitors of the enzyme family result in reduced cell surface Olinked glycosylation and induce apoptosis in cultured cells. Thus, a selective inhibitor of pp-GalNAc-T6 is likely to target cancer cells and could be developed into a novel anticancer therapy.

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Analysis of Carbohydrates and Glycoconjugates by Matrix‐assisted Laser Desorption/Ionization Mass Spectrometry: An Update for 2015–2016

Harvey

2021

Mass Spectrometry Reviews

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This review is the ninth update of the original article published in 1999 on the application of matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2016. Also included are papers that describe methods appropriate to analysis by MALDI, such as sample preparation techniques, even though the ionization method is not MALDI. Topics covered in the first part of the review include general aspects such as theory of the MALDI process, matrices, derivatization, MALDI imaging, fragmentation and arrays. The second part of the review is devoted to applications to various structural types such as oligo‐ and poly‐saccharides, glycoproteins, glycolipids, glycosides and biopharmaceuticals. Much of this material is presented in tabular form. The third part of the review covers medical and industrial applications of the technique, studies of enzyme reactions and applications to chemical synthesis. The reported work shows increasing use of combined new techniques such as ion mobility and the enormous impact that MALDI imaging is having. MALDI, although invented over 30 years ago is still an ideal technique for carbohydrate analysis and advancements in the technique and range of applications show no sign of deminishing. © 2020 Wiley Periodicals, Inc.

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Morphological Changes, Cadherin Switching, and Growth Suppression in Pancreatic Cancer by GALNT6 Knockdown

Cited by 32 publications

References 22 publications

De novo expression of human polypeptide N-acetylgalactosaminyltransferase 6 (GalNAc-T6) in colon adenocarcinoma inhibits the differentiation of colonic epithelium

De novo expression of human polypeptide N-acetylgalactosaminyltransferase 6 (GalNAc-T6) in colon adenocarcinoma inhibits the differentiation of colonic epithelium

UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase- 6 (pp-GalNAc-T6): Role in Cancer and Prospects as a Drug Target

Analysis of Carbohydrates and Glycoconjugates by Matrix‐assisted Laser Desorption/Ionization Mass Spectrometry: An Update for 2015–2016

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