Hexavalent chromium promotes malignant transformation via enhanced translation of SUV39H1

Authors

Yiwei Gu, University of Kentucky
Yanan Cao, University of KentuckyFollow
Qing Ye, University of KentuckyFollow
Yujing Zhang, University of Kentucky
Zhishan Wang, University of KentuckyFollow
Chengfeng Yang, University of KentuckyFollow
Side Liu, Southern Medical University (China)Follow
Qing-Bai She, University of KentuckyFollow

Abstract

Hexavalent chromium [Cr(VI)] is a widespread environmental carcinogen linked to lung cancer and other malignancies. Although genetic and epigenetic mechanisms of Cr(VI)-induced carcinogenesis have been extensively investigated, the role of translational control has remained largely unexplored. Here, we show that chronic low-dose Cr(VI) exposure in BEAS-2BR human bronchial epithelial cells activates eIF4E-driven cap-dependent translation through mTORC1-mediated phosphorylation and inactivation of the translational repressor 4E-BP1. Pharmacological inhibition of this pathway markedly suppresses Cr(VI)-induced cell transformation, cancer stem cell (CSC)-like properties, and DNA damage. Comparable inhibitory effects are observed following raptor knockdown, which disrupts mTORC1, or expression of a constitutively active non-phosphorylatable 4E-BP1 mutant. Notably, the histone methyltransferase SUV39H1 is selectively upregulated at the translational level and contributes to Cr(VI)-induced malignant phenotypes. Inhibition of the mTORC1/4E-BP1 signaling pathway, either pharmacologically or genetically, reduces SUV39H1 translation, whereas ectopic SUV39H1 expression restores CSC-like properties and DNA damage even in the presence of pathway inhibition. Together, these findings identify mTORC1/4E-BP1-mediated translational upregulation of SUV39H1 as an important mechanistic link in Cr(VI)-induced carcinogenesis, revealing a novel layer of regulation that integrates translational control with environmental carcinogen-induced epigenetic reprogramming.

Document Type

Article

Publication Date

2026

Notes/Citation Information

0009-2797/© 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.cbi.2025.111869

Funding Information

This work was supported in part by the Redox Metabolism Shared Resource Facility of the University of Kentucky Markey Cancer Center, United States (P30CA177558) and by start-up funds provided to Q.-B.S.

Repository Citation

Gu, Yiwei; Cao, Yanan; Ye, Qing; Zhang, Yujing; Wang, Zhishan; Yang, Chengfeng; Liu, Side; and She, Qing-Bai, "Hexavalent chromium promotes malignant transformation via enhanced translation of SUV39H1" (2026). Markey Cancer Center Faculty Publications. 473.
https://uknowledge.uky.edu/markey_facpub/473