Signaling pathway of globo-series glycosphingolipids and β1,3-galactosyltransferase V (β3GalT5) in breast cancer

Po Kai Chuang, Michael Hsiao, Tsui Ling Hsu, Chuan-Fa Chang, Chung Yi Wu, Bo Rui Chen, Han Wen Huang, Kuo Shiang Liao, Chen Chun Chen, Chi Long Chen, Shun Min Yang, Chiung Wen Kuo, Peilin Chen, Ping Tzu Chiu, I. Ju Chen, Jiann Shiun Lai, Cheng Der Tony Yu, Chi Huey Wong

Research output: Contribution to journalArticle

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Abstract

The globo-series glycosphingolipids (GSLs) SSEA3, SSEA4, an Globo-H specifically expressed on cancer cells are found to correlat with tumor progression and metastasis, but the functional role of these GSLs and the key enzyme β1,3-galactosyltransferase (β3GalT5) that converts Gb4 to SSEA3 remain largely unclear. Her we show that the expression of β3GalT5 significantly correlates wit tumor progression and poor survival in patients, and the globo series GSLs in breast cancer cells form a complex in membrane lipi raft with caveolin-1 (CAV1) and focal adhesion kinase (FAK) whic then interact with AKT and receptor-interacting protein kinase (RIP) respectively. Knockdown of β3GalT5 disrupts the complex and in duces apoptosis through dissociation of RIP from the complex t interact with the Fas death domain (FADD) and trigger the Fas dependent pathway. This finding provides a link between SSEA3 SSEA4/Globo-H and the FAK/CAV1/AKT/RIP complex in tumor pro gression and apoptosis and suggests a direction for the treatment o breast cancer, as demonstrated by the combined use of antibodie against Globo-H and SSEA4.

Original languageEnglish
Pages (from-to)3518-3523
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number9
DOIs
Publication statusPublished - 2019 Feb 26

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Galactosyltransferases
Glycosphingolipids
Receptor-Interacting Protein Serine-Threonine Kinases
Protein Kinases
Breast Neoplasms
Caveolin 1
Focal Adhesion Kinase 1
Neoplasms
Apoptosis
Focal Adhesion Protein-Tyrosine Kinases
Wit and Humor
Neoplasm Metastasis
Membranes
Survival
Enzymes
Globo-H

All Science Journal Classification (ASJC) codes

  • General

Cite this

Chuang, Po Kai ; Hsiao, Michael ; Hsu, Tsui Ling ; Chang, Chuan-Fa ; Wu, Chung Yi ; Chen, Bo Rui ; Huang, Han Wen ; Liao, Kuo Shiang ; Chen, Chen Chun ; Chen, Chi Long ; Yang, Shun Min ; Kuo, Chiung Wen ; Chen, Peilin ; Chiu, Ping Tzu ; Chen, I. Ju ; Lai, Jiann Shiun ; Yu, Cheng Der Tony ; Wong, Chi Huey. / Signaling pathway of globo-series glycosphingolipids and β1,3-galactosyltransferase V (β3GalT5) in breast cancer. In: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; Vol. 116, No. 9. pp. 3518-3523.
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title = "Signaling pathway of globo-series glycosphingolipids and β1,3-galactosyltransferase V (β3GalT5) in breast cancer",
abstract = "The globo-series glycosphingolipids (GSLs) SSEA3, SSEA4, an Globo-H specifically expressed on cancer cells are found to correlat with tumor progression and metastasis, but the functional role of these GSLs and the key enzyme β1,3-galactosyltransferase (β3GalT5) that converts Gb4 to SSEA3 remain largely unclear. Her we show that the expression of β3GalT5 significantly correlates wit tumor progression and poor survival in patients, and the globo series GSLs in breast cancer cells form a complex in membrane lipi raft with caveolin-1 (CAV1) and focal adhesion kinase (FAK) whic then interact with AKT and receptor-interacting protein kinase (RIP) respectively. Knockdown of β3GalT5 disrupts the complex and in duces apoptosis through dissociation of RIP from the complex t interact with the Fas death domain (FADD) and trigger the Fas dependent pathway. This finding provides a link between SSEA3 SSEA4/Globo-H and the FAK/CAV1/AKT/RIP complex in tumor pro gression and apoptosis and suggests a direction for the treatment o breast cancer, as demonstrated by the combined use of antibodie against Globo-H and SSEA4.",
author = "Chuang, {Po Kai} and Michael Hsiao and Hsu, {Tsui Ling} and Chuan-Fa Chang and Wu, {Chung Yi} and Chen, {Bo Rui} and Huang, {Han Wen} and Liao, {Kuo Shiang} and Chen, {Chen Chun} and Chen, {Chi Long} and Yang, {Shun Min} and Kuo, {Chiung Wen} and Peilin Chen and Chiu, {Ping Tzu} and Chen, {I. Ju} and Lai, {Jiann Shiun} and Yu, {Cheng Der Tony} and Wong, {Chi Huey}",
year = "2019",
month = "2",
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Chuang, PK, Hsiao, M, Hsu, TL, Chang, C-F, Wu, CY, Chen, BR, Huang, HW, Liao, KS, Chen, CC, Chen, CL, Yang, SM, Kuo, CW, Chen, P, Chiu, PT, Chen, IJ, Lai, JS, Yu, CDT & Wong, CH 2019, 'Signaling pathway of globo-series glycosphingolipids and β1,3-galactosyltransferase V (β3GalT5) in breast cancer', Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 9, pp. 3518-3523. https://doi.org/10.1073/pnas.1816946116

Signaling pathway of globo-series glycosphingolipids and β1,3-galactosyltransferase V (β3GalT5) in breast cancer. / Chuang, Po Kai; Hsiao, Michael; Hsu, Tsui Ling; Chang, Chuan-Fa; Wu, Chung Yi; Chen, Bo Rui; Huang, Han Wen; Liao, Kuo Shiang; Chen, Chen Chun; Chen, Chi Long; Yang, Shun Min; Kuo, Chiung Wen; Chen, Peilin; Chiu, Ping Tzu; Chen, I. Ju; Lai, Jiann Shiun; Yu, Cheng Der Tony; Wong, Chi Huey.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, No. 9, 26.02.2019, p. 3518-3523.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Signaling pathway of globo-series glycosphingolipids and β1,3-galactosyltransferase V (β3GalT5) in breast cancer

AU - Chuang, Po Kai

AU - Hsiao, Michael

AU - Hsu, Tsui Ling

AU - Chang, Chuan-Fa

AU - Wu, Chung Yi

AU - Chen, Bo Rui

AU - Huang, Han Wen

AU - Liao, Kuo Shiang

AU - Chen, Chen Chun

AU - Chen, Chi Long

AU - Yang, Shun Min

AU - Kuo, Chiung Wen

AU - Chen, Peilin

AU - Chiu, Ping Tzu

AU - Chen, I. Ju

AU - Lai, Jiann Shiun

AU - Yu, Cheng Der Tony

AU - Wong, Chi Huey

PY - 2019/2/26

Y1 - 2019/2/26

N2 - The globo-series glycosphingolipids (GSLs) SSEA3, SSEA4, an Globo-H specifically expressed on cancer cells are found to correlat with tumor progression and metastasis, but the functional role of these GSLs and the key enzyme β1,3-galactosyltransferase (β3GalT5) that converts Gb4 to SSEA3 remain largely unclear. Her we show that the expression of β3GalT5 significantly correlates wit tumor progression and poor survival in patients, and the globo series GSLs in breast cancer cells form a complex in membrane lipi raft with caveolin-1 (CAV1) and focal adhesion kinase (FAK) whic then interact with AKT and receptor-interacting protein kinase (RIP) respectively. Knockdown of β3GalT5 disrupts the complex and in duces apoptosis through dissociation of RIP from the complex t interact with the Fas death domain (FADD) and trigger the Fas dependent pathway. This finding provides a link between SSEA3 SSEA4/Globo-H and the FAK/CAV1/AKT/RIP complex in tumor pro gression and apoptosis and suggests a direction for the treatment o breast cancer, as demonstrated by the combined use of antibodie against Globo-H and SSEA4.

AB - The globo-series glycosphingolipids (GSLs) SSEA3, SSEA4, an Globo-H specifically expressed on cancer cells are found to correlat with tumor progression and metastasis, but the functional role of these GSLs and the key enzyme β1,3-galactosyltransferase (β3GalT5) that converts Gb4 to SSEA3 remain largely unclear. Her we show that the expression of β3GalT5 significantly correlates wit tumor progression and poor survival in patients, and the globo series GSLs in breast cancer cells form a complex in membrane lipi raft with caveolin-1 (CAV1) and focal adhesion kinase (FAK) whic then interact with AKT and receptor-interacting protein kinase (RIP) respectively. Knockdown of β3GalT5 disrupts the complex and in duces apoptosis through dissociation of RIP from the complex t interact with the Fas death domain (FADD) and trigger the Fas dependent pathway. This finding provides a link between SSEA3 SSEA4/Globo-H and the FAK/CAV1/AKT/RIP complex in tumor pro gression and apoptosis and suggests a direction for the treatment o breast cancer, as demonstrated by the combined use of antibodie against Globo-H and SSEA4.

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