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

被引：11

作者：

Shih, Pei-Chun ^{[1
,2
]}

Chen, Hsin-Pao ^{[3
,4
]}

Hsu, Ching-Cheng ^{[1
,2
,5
]}

Lin, Chung-Hsien ^{[1
,2
]}

Ko, Chou-Yuan ^{[6
,7
]}

Hsueh, Chao -Wen ^{[6
,7
]}

Huang, Cheng-Yi ^{[7
,8
]}

Chu, Tian-Huei ^{[7
,13
]}

Wu, Cheng-Chun ^{[4
]}

Ho, Yu-Cheng ^{[4
]}

Nguyen, Ngoc Uyen Nhi ^{[5
]}

Huang, Shih-Chung ^{[7
,9
,13
]}

Fang, Cheng-Chieh ^{[10
]}

Tzou, Shiow-Jyu ^{[7
,11
,13
]}

Wu, Yueh-Jung ^{[12
]}

Chen, Tung -Yuan ^{[12
]}

Chang, Chuan-Fa ^{[1
,2
]}

Lee, Yung-Kuo ^{[7
,13
]}

机构：

[1] Natl Cheng Kung Univ, Inst Basic Med Sci, Coll Med, Tainan 70101, Taiwan

[2] Natl Cheng Kung Univ, Coll Med, Dept Med Lab Sci & Biotechnol, Tainan 70101, Taiwan

[3] I Shou Univ, E DA Hosp, Dept Surg, Div Colon & Rectal Surg, Kaohsiung 82445, Taiwan

[4] I Shou Univ, Coll Med, Sch Med, Kaohsiung 82445, Taiwan

[5] Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Div Cardiol, Dallas, TX 75390 USA

[6] Kaohsiung Armed Forces Gen Hosp, Dept Internal Med, Div Gastroenterol & Hepatol, Kaohsiung 80284, Taiwan

[7] Natl Sun Yat Sen Univ, Inst Med Sci & Technol, Kaohsiung 80424, Taiwan

[8] Kaohsiung Armed Forces Gen Hosp, Dept Pathol, Kaohsiung 80284, Taiwan

[9] Kaohsiung Armed Forces Gen Hosp, Dept Med, Div Cardiol, Kaohsiung 80284, Taiwan

[10] Primo Biotechnol Co Ltd, Taipei 104511, Taiwan

[11] Kaohsiung Armed Forces Gen Hosp, Dept Nursing, Kaohsiung 80284, Taiwan

[12] Kaohsiung Armed Forces Gen Hosp, Dept Surg, Div Colorectal Surg, Kaohsiung 80284, Taiwan

[13] Kaohsiung Armed Forces Gen Hosp, Med Educ & Res Ctr, Med Lab, Kaohsiung 80284, Taiwan

来源：

ENVIRONMENTAL POLLUTION | 2023年 / 327卷

关键词：

Long-term phthalates exposure; Environmental pollution; Colorectal cancer; Oncogenic risks; Glycosylation alterations; ST8SIA6; DIETHYLHEXYL PHTHALATE; GENE-EXPRESSION; GLYCOPROTEIN; MARKER; GROWTH;

D O I：

10.1016/j.envpol.2023.121476

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

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 longterm plasticizers exposure. First, we determined the profiles of cell surface N-glycomes by using mass spectrometry and found out the alterations of alpha 2,8-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.

引用

页数：13

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