Long-term DEHP/MEHP exposure promotes colorectal cancer stemness associated with glycosylation alterations

Pei Chun Shih; Hsin Pao Chen; Ching Cheng Hsu; Chung Hsien Lin; Chou Yuan Ko; Chao Wen Hsueh; Cheng Yi Huang; Tian Huei Chu; Cheng Chun Wu; Yu Cheng Ho; Ngoc Uyen Nhi Nguyen; Shih Chung Huang; Cheng Chieh Fang; Shiow Jyu Tzou; Yueh Jung Wu; Tung Yuan Chen; Chuan Fa Chang; Yung Kuo Lee

doi:10.1016/j.envpol.2023.121476

Long-term DEHP/MEHP exposure promotes colorectal cancer stemness associated with glycosylation alterations

Pei Chun Shih, Hsin Pao Chen, Ching Cheng Hsu, Chung Hsien Lin, Chou Yuan Ko, Chao Wen Hsueh, Cheng Yi Huang, Tian Huei Chu, Cheng Chun Wu, Yu Cheng Ho, Ngoc Uyen Nhi Nguyen, Shih Chung Huang, Cheng Chieh Fang, Shiow Jyu Tzou, Yueh Jung Wu, Tung Yuan Chen, Chuan Fa Chang, Yung Kuo Lee

Department of Medical Laboratory Science and Biotechnology

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

Abstract

Plasticizers are considered as environmental pollution released from medical devices and increased potential oncogenic risks in clinical therapy. Our previous studies have shown that long-term exposure to di-ethylhexyl phthalate (DEHP)/mono-ethylhexyl phthalate (MEHP) promotes chemotherapeutic drug resistance in colorectal cancer. In this study, we investigated the alteration of glycosylation in colorectal cancer following long-term plasticizers exposure. First, we determined the profiles of cell surface N-glycomes by using mass spectrometry and found out the alterations of α2,8-linkages glycans. Next, we analyzed the correlation between serum DEHP/MEHP levels and ST8SIA6 expression from matched tissues in total 110 colorectal cancer patients. Moreover, clinical specimens and TCGA database were used to analyze the expression of ST8SIA6 in advanced stage of cancer. Finally, we showed that ST8SIA6 regulated stemness in vitro and in vivo. Our results revealed long-term DEHP/MEHP exposure significantly caused cancer patients with poorer survival outcome and attenuated the expression of ST8SIA6 in cancer cells and tissue samples. As expected, silencing of ST8SIA6 promoted cancer stemness and tumorigenicity by upregulating stemness-associated proteins. In addition, the cell viability assay showed enhanced drug resistance in ST8SIA6 silencing cells treated with irinotecan. Besides, ST8SIA6 was downregulated in the advanced stage and positively correlated with tumor recurrence in colorectal cancer. Our results imply that ST8SIA6 potentially plays an important role in oncogenic effects with long-term phthalates exposure.

Original language	English
Article number	121476
Journal	Environmental Pollution
Volume	327
DOIs	https://doi.org/10.1016/j.envpol.2023.121476
Publication status	Published - 2023 Jun 15

All Science Journal Classification (ASJC) codes

Toxicology
Pollution
Health, Toxicology and Mutagenesis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.envpol.2023.121476

Cite this

Shih, P. C., Chen, H. P., Hsu, C. C., Lin, C. H., Ko, C. Y., Hsueh, C. W., Huang, C. Y., Chu, T. H., Wu, C. C., Ho, Y. C., Nguyen, N. U. N., Huang, S. C., Fang, C. C., Tzou, S. J., Wu, Y. J., Chen, T. Y., Chang, C. F., & Lee, Y. K. (2023). Long-term DEHP/MEHP exposure promotes colorectal cancer stemness associated with glycosylation alterations. Environmental Pollution, 327, Article 121476. https://doi.org/10.1016/j.envpol.2023.121476

@article{ffcee9ac1db14790bea04da5925b2efe,

title = "Long-term DEHP/MEHP exposure promotes colorectal cancer stemness associated with glycosylation alterations",

abstract = "Plasticizers are considered as environmental pollution released from medical devices and increased potential oncogenic risks in clinical therapy. Our previous studies have shown that long-term exposure to di-ethylhexyl phthalate (DEHP)/mono-ethylhexyl phthalate (MEHP) promotes chemotherapeutic drug resistance in colorectal cancer. In this study, we investigated the alteration of glycosylation in colorectal cancer following long-term plasticizers exposure. First, we determined the profiles of cell surface N-glycomes by using mass spectrometry and found out the alterations of α2,8-linkages glycans. Next, we analyzed the correlation between serum DEHP/MEHP levels and ST8SIA6 expression from matched tissues in total 110 colorectal cancer patients. Moreover, clinical specimens and TCGA database were used to analyze the expression of ST8SIA6 in advanced stage of cancer. Finally, we showed that ST8SIA6 regulated stemness in vitro and in vivo. Our results revealed long-term DEHP/MEHP exposure significantly caused cancer patients with poorer survival outcome and attenuated the expression of ST8SIA6 in cancer cells and tissue samples. As expected, silencing of ST8SIA6 promoted cancer stemness and tumorigenicity by upregulating stemness-associated proteins. In addition, the cell viability assay showed enhanced drug resistance in ST8SIA6 silencing cells treated with irinotecan. Besides, ST8SIA6 was downregulated in the advanced stage and positively correlated with tumor recurrence in colorectal cancer. Our results imply that ST8SIA6 potentially plays an important role in oncogenic effects with long-term phthalates exposure.",

author = "Shih, {Pei Chun} and Chen, {Hsin Pao} and Hsu, {Ching Cheng} and Lin, {Chung Hsien} and Ko, {Chou Yuan} and Hsueh, {Chao Wen} and Huang, {Cheng Yi} and Chu, {Tian Huei} and Wu, {Cheng Chun} and Ho, {Yu Cheng} and Nguyen, {Ngoc Uyen Nhi} and Huang, {Shih Chung} and Fang, {Cheng Chieh} and Tzou, {Shiow Jyu} and Wu, {Yueh Jung} and Chen, {Tung Yuan} and Chang, {Chuan Fa} and Lee, {Yung Kuo}",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier Ltd",

year = "2023",

month = jun,

day = "15",

doi = "10.1016/j.envpol.2023.121476",

language = "English",

volume = "327",

journal = "Environmental Pollution",

issn = "0269-7491",

publisher = "Elsevier Limited",

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Shih, PC, Chen, HP, Hsu, CC, Lin, CH, Ko, CY, Hsueh, CW, Huang, CY, Chu, TH, Wu, CC, Ho, YC, Nguyen, NUN, Huang, SC, Fang, CC, Tzou, SJ, Wu, YJ, Chen, TY, Chang, CF & Lee, YK 2023, 'Long-term DEHP/MEHP exposure promotes colorectal cancer stemness associated with glycosylation alterations', Environmental Pollution, vol. 327, 121476. https://doi.org/10.1016/j.envpol.2023.121476

TY - JOUR

T1 - Long-term DEHP/MEHP exposure promotes colorectal cancer stemness associated with glycosylation alterations

AU - Shih, Pei Chun

AU - Chen, Hsin Pao

AU - Hsu, Ching Cheng

AU - Lin, Chung Hsien

AU - Ko, Chou Yuan

AU - Hsueh, Chao Wen

AU - Huang, Cheng Yi

AU - Chu, Tian Huei

AU - Wu, Cheng Chun

AU - Ho, Yu Cheng

AU - Nguyen, Ngoc Uyen Nhi

AU - Huang, Shih Chung

AU - Fang, Cheng Chieh

AU - Tzou, Shiow Jyu

AU - Wu, Yueh Jung

AU - Chen, Tung Yuan

AU - Chang, Chuan Fa

AU - Lee, Yung Kuo

PY - 2023/6/15

Y1 - 2023/6/15

N2 - Plasticizers are considered as environmental pollution released from medical devices and increased potential oncogenic risks in clinical therapy. Our previous studies have shown that long-term exposure to di-ethylhexyl phthalate (DEHP)/mono-ethylhexyl phthalate (MEHP) promotes chemotherapeutic drug resistance in colorectal cancer. In this study, we investigated the alteration of glycosylation in colorectal cancer following long-term plasticizers exposure. First, we determined the profiles of cell surface N-glycomes by using mass spectrometry and found out the alterations of α2,8-linkages glycans. Next, we analyzed the correlation between serum DEHP/MEHP levels and ST8SIA6 expression from matched tissues in total 110 colorectal cancer patients. Moreover, clinical specimens and TCGA database were used to analyze the expression of ST8SIA6 in advanced stage of cancer. Finally, we showed that ST8SIA6 regulated stemness in vitro and in vivo. Our results revealed long-term DEHP/MEHP exposure significantly caused cancer patients with poorer survival outcome and attenuated the expression of ST8SIA6 in cancer cells and tissue samples. As expected, silencing of ST8SIA6 promoted cancer stemness and tumorigenicity by upregulating stemness-associated proteins. In addition, the cell viability assay showed enhanced drug resistance in ST8SIA6 silencing cells treated with irinotecan. Besides, ST8SIA6 was downregulated in the advanced stage and positively correlated with tumor recurrence in colorectal cancer. Our results imply that ST8SIA6 potentially plays an important role in oncogenic effects with long-term phthalates exposure.

AB - Plasticizers are considered as environmental pollution released from medical devices and increased potential oncogenic risks in clinical therapy. Our previous studies have shown that long-term exposure to di-ethylhexyl phthalate (DEHP)/mono-ethylhexyl phthalate (MEHP) promotes chemotherapeutic drug resistance in colorectal cancer. In this study, we investigated the alteration of glycosylation in colorectal cancer following long-term plasticizers exposure. First, we determined the profiles of cell surface N-glycomes by using mass spectrometry and found out the alterations of α2,8-linkages glycans. Next, we analyzed the correlation between serum DEHP/MEHP levels and ST8SIA6 expression from matched tissues in total 110 colorectal cancer patients. Moreover, clinical specimens and TCGA database were used to analyze the expression of ST8SIA6 in advanced stage of cancer. Finally, we showed that ST8SIA6 regulated stemness in vitro and in vivo. Our results revealed long-term DEHP/MEHP exposure significantly caused cancer patients with poorer survival outcome and attenuated the expression of ST8SIA6 in cancer cells and tissue samples. As expected, silencing of ST8SIA6 promoted cancer stemness and tumorigenicity by upregulating stemness-associated proteins. In addition, the cell viability assay showed enhanced drug resistance in ST8SIA6 silencing cells treated with irinotecan. Besides, ST8SIA6 was downregulated in the advanced stage and positively correlated with tumor recurrence in colorectal cancer. Our results imply that ST8SIA6 potentially plays an important role in oncogenic effects with long-term phthalates exposure.

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U2 - 10.1016/j.envpol.2023.121476

DO - 10.1016/j.envpol.2023.121476

M3 - Article

C2 - 36997141

AN - SCOPUS:85151555655

SN - 0269-7491

VL - 327

JO - Environmental Pollution

JF - Environmental Pollution

M1 - 121476

ER -

Long-term DEHP/MEHP exposure promotes colorectal cancer stemness associated with glycosylation alterations

Abstract

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