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The sialyl-Tn antigen synthase genes regulates migration–proliferation dichotomy in prostate cancer cells under hypoxia

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Abstract

A low-oxygen (hypoxia) tumor microenvironment can facilitate chemotherapy and radiation therapy resistance in tumors and is associated with a poor prognosis. Hypoxia also affects PCa (prostate cancer) phenotype transformation and causes therapeutic resistance. Although O-glycans are known to be involved in the malignancy of various cancers under hypoxia, the expression and function of O-glycans in PCa are not well understood. In this study, the saccharide primer method was employed to analyze O-glycan expression in PCa cells. Results showed that the expression of sTn antigens was increased in PCa cells under hypoxia. Furthermore, it was found that ST6GalNAc1, the sTn antigen synthase gene, was involved in the migration–proliferation dichotomy and drug resistance in PCa cells under hypoxia. The results of this study will contribute to the development of novel diagnostic markers and drug targets for PCa under hypoxia.

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Data availability

All data generated or analyzed in this study are included in this article and its supplemental information files.

Abbreviations

TME:

Tumor microenvironment

HIF-1α:

Hypoxia-inducible factor α

PCa:

Prostate cancer

CRPC:

Castration-resistant prostate cancer

Asn:

Asparagine

Thr:

Threonine

LC-MS:

Liquid chromatography-mass spectrometry

GalNAc:

N-Acetylgalactosamine

GlcNAc:

N-Acetylglucosamine

sTn:

Sialyl-Tn

C1GalT1:

glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase

GCNT3:

β-1,6-N-Acetylglucosaminyltransferase gene 3

ST6GalNAc1:

ST6 N-acetylgalactosaminide α-2,6-sialyltransferase 1

B3GALT5:

β-1,3-Galactosyltransferase 5

B4GALT1/5:

β-1,4-Galactosyltransferase 1/5

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

EGFR:

Epidermal growth factor receptor

MDR:

Multidrug resistance

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Acknowledgements

We would like to thank Editage (www.editage.com) for English language editing.

Funding

This work was partly supported by MEXT-Supported Program for the Strategic Research Foundation at Private Universities (S1411003 to TS) and JSPS KAKENHI (JP23241075 to T.S.), Japan.

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Authors and Affiliations

  1. Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 223-8522, Kanagawa, Japan

    Daiki Yamamoto & Toshinori Sato

  2. Department of Urology, Keio University School of Medicine, 160-8582, Tokyo, Japan

    Hiroshi Hongo, Takeo Kosaka, Natsumi Aoki & Mototsugu Oya

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  1. Daiki Yamamoto
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  2. Hiroshi Hongo
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  3. Takeo Kosaka
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  4. Natsumi Aoki
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  6. Toshinori Sato
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Contributions

Daiki Yamamoto and Toshinori Sato conceived and planned the experiments, and wrote the main manuscript text. Takeo Kosaka, Hiroshi Hongo and Mototsugu Oya helped supervise the project and contributed analysis tools. Daiki Yamamoto carried out the experiment, and Natsumi Aoki contributed sample preparation. All authors reviewed the manuscript.

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Correspondence to Toshinori Sato.

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Yamamoto, D., Hongo, H., Kosaka, T. et al. The sialyl-Tn antigen synthase genes regulates migration–proliferation dichotomy in prostate cancer cells under hypoxia. Glycoconj J 40, 199–212 (2023). https://doi.org/10.1007/s10719-023-10104-z

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