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Suppression of vitamin D metabolizing enzyme CYP24A1 provides increased sensitivity to chemotherapeutic drugs in breast cancer

Sakura Kamiya, Nakamori Yuna, Akira Takasawa, Kumi Takasawa, View ORCID ProfileDaisuke Kyuno, Yusuke Ono, Kazufumi Magara, Makoto Osanai
doi: https://doi.org/10.1101/2022.10.18.512762
Sakura Kamiya
1Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan
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Nakamori Yuna
1Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan
2Department of Oral Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan
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Akira Takasawa
1Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan
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Kumi Takasawa
1Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan
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Daisuke Kyuno
1Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan
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  • ORCID record for Daisuke Kyuno
Yusuke Ono
1Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan
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Kazufumi Magara
1Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan
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Makoto Osanai
1Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan
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  • For correspondence: osanaim@sapmed.ac.jp
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Abstract

Vitamin D is an essential nutrient for the human body that plays an important role in homeostasis and contributes to cell fate decision including proliferation, differentiation and cell viability. Accumulated epidemiological data suggest a relationship between vitamin D deficiency and carcinogenesis in various organs. However, the underlying mechanism remains to be further clarified. In this study, we showed that vitamin D metabolizing enzyme CYP24A1 promotes the oncogenic property of breast carcinoma cells. In addition, expression of CYP24A1 is elevated in invasive breast carcinoma and decreases the overall survival. Importantly, CYP24A1 suppression significantly enhances cell death sensitivity to two pharmacologically different acting anticancer drugs, cisplatin and gefitinib. The results of our study suggest the possibility of CYP24A1-inhibiting therapy for breast malignancy.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted October 21, 2022.
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Suppression of vitamin D metabolizing enzyme CYP24A1 provides increased sensitivity to chemotherapeutic drugs in breast cancer
Sakura Kamiya, Nakamori Yuna, Akira Takasawa, Kumi Takasawa, Daisuke Kyuno, Yusuke Ono, Kazufumi Magara, Makoto Osanai
bioRxiv 2022.10.18.512762; doi: https://doi.org/10.1101/2022.10.18.512762
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Suppression of vitamin D metabolizing enzyme CYP24A1 provides increased sensitivity to chemotherapeutic drugs in breast cancer
Sakura Kamiya, Nakamori Yuna, Akira Takasawa, Kumi Takasawa, Daisuke Kyuno, Yusuke Ono, Kazufumi Magara, Makoto Osanai
bioRxiv 2022.10.18.512762; doi: https://doi.org/10.1101/2022.10.18.512762

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