title: Chromium IV exposure, via Src/Ras signaling, promotes cell transformation.
abstract: Hexavalent chromium [Cr(VI)] is a well-known environment carcinogen. The exposure of Cr(VI) through contaminated soil, air particles, and drinking water is a strong concern for the public health worldwide. While many studies have been done, it remains unclear which intracellular molecules transduce Cr(VI)-mediated carcinogenic signaling in cells to promote cancer. In this study, we demonstrated that upon Cr(VI) treatment, the intracellular receptor src was activated, which further upregulated Ras activity, leading to the augmentation of ROS and onset of ER stress in human lung epithelial BEAS-2B or keratinocytes. These cells were formed colonies in soft agar cultures following the persistent Cr(VI) treatment. Furthermore, anti-apoptotic factor Bcl-2 was upregulated and activated in the colonies. Thus, our study suggests that Cr(VI), though activating the src and Ras signaling axis, perturbs redox state and invokes ER stress for the establishment of carcinogenic actions in the cells. In this process, Bcl-2 appears playing an important role. By uncovering these intracellular targets, our study may help developing novel strategies for better environmental protection, especially in areas contaminated or polluted by Cr(VI) as well as for effective cancer treatments.
authors.affiliation: Center for Drug Development, Northeastern University, Boston, Massachusetts.
authors.forename: Suthakar
authors.identifier: 0000-0001-8565-4561
authors.initials: S
authors.lastname: Ganapathy
authors.affiliation: The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.|The Institute of Clinic Sciences, Sahlgrenska Academy, Gothenburg, Sweden.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Center for Drug Development, Northeastern University, Boston, Massachusetts.
authors.forename: Jean
authors.initials: J
authors.lastname: Lafontant
authors.affiliation: The Institute of Clinic Sciences, Sahlgrenska Academy, Gothenburg, Sweden.
authors.forename: Rui
authors.initials: R
authors.lastname: Xiong
authors.affiliation: Center for Drug Development, Northeastern University, Boston, Massachusetts.
authors.forename: Tianqi
authors.initials: T
authors.lastname: Yu
authors.affiliation: The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Center for Drug Development, Northeastern University, Boston, Massachusetts.
authors.forename: Changyan
authors.initials: C
authors.lastname: Chen
mesh_terms: D002274:Carcinogens, Environmental / Q000009:adverse effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D002857:Chromium / Q000009:adverse effects*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D018631:ras Proteins / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D002274:Carcinogens, Environmental; D017382:Reactive Oxygen Species; D002857:Chromium; C074702:chromium hexavalent ion; D019061:src-Family Kinases; D018631:ras Proteins
keywords: Cr(VI); ROS; Ras; carcinogenesis; src