Journal article
Ping Yang, Jie Xie, Yunfei Li, Hsuan-Pei Lin, William Fenske, M. Clementino, Yiguo Jiang, Chengfeng Yang, Zhishan Wang
Theranostics, 2020
Theranostics, 2020
Semantic Scholar
DOI
PubMedCentral
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APA
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Yang, P., Xie, J., Li, Y., Lin, H.-P., Fenske, W., Clementino, M., … Wang, Z. (2020). Deubiquitinase USP7-mediated MCL-1 up-regulation enhances Arsenic and Benzo(a)pyrene co-exposure-induced Cancer Stem Cell-like property and Tumorigenesis. Theranostics.
Chicago/Turabian
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Yang, Ping, Jie Xie, Yunfei Li, Hsuan-Pei Lin, William Fenske, M. Clementino, Yiguo Jiang, Chengfeng Yang, and Zhishan Wang. “Deubiquitinase USP7-Mediated MCL-1 up-Regulation Enhances Arsenic and Benzo(a)Pyrene Co-Exposure-Induced Cancer Stem Cell-like Property and Tumorigenesis.” Theranostics (2020).
MLA
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Yang, Ping, et al. “Deubiquitinase USP7-Mediated MCL-1 up-Regulation Enhances Arsenic and Benzo(a)Pyrene Co-Exposure-Induced Cancer Stem Cell-like Property and Tumorigenesis.” Theranostics, 2020.
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@article{ping2020a,
title = {Deubiquitinase USP7-mediated MCL-1 up-regulation enhances Arsenic and Benzo(a)pyrene co-exposure-induced Cancer Stem Cell-like property and Tumorigenesis},
year = {2020},
journal = {Theranostics},
author = {Yang, Ping and Xie, Jie and Li, Yunfei and Lin, Hsuan-Pei and Fenske, William and Clementino, M. and Jiang, Yiguo and Yang, Chengfeng and Wang, Zhishan}
}
Abstract
Rationale: MCL-1 is up-regulated in cancer and a target for cancer treatment. How MCL-1 is up-regulated and whether MCL-1 up-regulation plays a role in tumorigenic process is not well-known. Arsenic and benzo(a)pyrene (BaP) are well-recognized lung carcinogens and we recently reported that arsenic and BaP co-exposure acts synergistically in inducing cancer stem cell (CSC)-like property and lung tumorigenesis. This study was performed to further investigate the underlying mechanism focusing on the role of MCL-1. Methods: The spheroid formation assay and nude mouse tumorigenesis assay were used to determine the CSC-like property and tumorigenicity of arsenic plus BaP co-exposure-transformed human bronchial epithelial BEAS-2B cells, respectively. Biochemical, pharmacological and genetic approaches were used to manipulate gene expressions, dissect signaling pathways and determine protein-protein interactions. Both loss-of-function and gain-of-function approaches were used to validate the role of MCL-1 in arsenic plus BaP co-exposure-enhanced CSC-like property and tumorigenicity. Results: Arsenic plus BaP co-exposure-transformed cells express significantly higher protein levels of MCL-1 than the passage-matched control, arsenic or BaP exposure alone-transformed cells. Knocking down MCL-1 levels in arsenic plus BaP co-exposure-transformed cells significantly reduced their apoptosis resistance, CSC-like property and tumorigenicity in mice. Mechanistic studies revealed that arsenic plus BaP co-exposure up-regulates MCL-1 protein levels by synergistically activating the PI3K/Akt/mTOR pathway to increase the level of a deubiquitinase USP7, which in turn reduces the level of MCL-1 protein ubiquitination and prevents its subsequent proteasome degradation. Conclusions: The deubiquitinase USP7-mediated MCL-1 up-regulation enhances arsenic and BaP co-exposure-induced CSC-like property and tumorigenesis, providing the first evidence demonstrating that USP7 stabilizes MCL-1 protein during the tumorigenic process.
