Chromium (VI) promotes lung cancer initiation by activating EGF/ALDH1A1 signalling
Abstract Lung cancer is the leading cause of cancer‐related death worldwide and is strongly associated with tobacco smoke exposure. Although smoking remains the most important and best studied risk factor, recent data suggest that several other carcinogens have a driving role in lung cancer developm...
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| Format: | Article |
| Language: | English |
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Wiley
2022-12-01
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| Series: | Clinical and Translational Discovery |
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| Online Access: | https://doi.org/10.1002/ctd2.155 |
| _version_ | 1797852219618361344 |
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| author | Anastasia E. Metropulos Jeffrey H. Becker Daniel R. Principe |
| author_facet | Anastasia E. Metropulos Jeffrey H. Becker Daniel R. Principe |
| author_sort | Anastasia E. Metropulos |
| collection | DOAJ |
| description | Abstract Lung cancer is the leading cause of cancer‐related death worldwide and is strongly associated with tobacco smoke exposure. Although smoking remains the most important and best studied risk factor, recent data suggest that several other carcinogens have a driving role in lung cancer development, particularly in select populations at risk of high or prolonged exposure. Hexavalent chromium [Cr(VI)] is a known carcinogen that is widely used in the manufacturing industry. While the link between Cr(VI) and lung cancer incidence is well‐accepted, the mechanisms through which Cr(VI) promotes lung cancer development are poorly understood. In the present study by Ge and colleagues published in Clinical and Translational Medicine, the authors explored the effects of prolonged Cr(VI) on non‐malignant lung epithelial cells. They determined that Cr(VI) initiates lung tumourigenesis by transforming a subpopulation of stem‐like, tumour initiating cells with increased expression of Aldehyde dehydrogenase 1 family member A1 (ALDH1A1). The observed increase in ALDH1A1 was dependent on transcriptional upregulation via Krüppel‐like factor 4 and associated with enhanced epidermal growth factor biosynthesis. Cr(VI)‐transformed tumour initiating cells accelerated tumour formation in vivo, which was ameliorated by therapeutic inhibition of ALDH1A1. Importantly, ALDH1A1 inhibition also sensitized Cr(VI)‐driven tumours to Gemcitabine chemotherapy and extended overall survival in mice. This study not only offers novel insight into the mechanisms through which Cr(VI) exposure initiates lung tumourigenesis but identifies a potential therapeutic target for patients with lung cancer secondary to Cr(VI) exposure. Additionally, this study underscores the importance of limiting exposure to Cr(VI) in the workplace and finding safer alternatives for use in the manufacturing industry. |
| first_indexed | 2024-04-09T19:30:30Z |
| format | Article |
| id | doaj.art-ecce47355f3b4901837f4ecf707a6412 |
| institution | Directory Open Access Journal |
| issn | 2768-0622 |
| language | English |
| last_indexed | 2024-04-09T19:30:30Z |
| publishDate | 2022-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Discovery |
| spelling | doaj.art-ecce47355f3b4901837f4ecf707a64122023-04-05T04:47:06ZengWileyClinical and Translational Discovery2768-06222022-12-0124n/an/a10.1002/ctd2.155Chromium (VI) promotes lung cancer initiation by activating EGF/ALDH1A1 signallingAnastasia E. Metropulos0Jeffrey H. Becker1Daniel R. Principe2Feinberg School of Medicine Northwestern University Chicago Illinois USADepartment of Surgery University of Illinois at Chicago Chicago Illinois USAMedical Scientist Training Program University of Illinois College of Medicine Chicago Illinois USAAbstract Lung cancer is the leading cause of cancer‐related death worldwide and is strongly associated with tobacco smoke exposure. Although smoking remains the most important and best studied risk factor, recent data suggest that several other carcinogens have a driving role in lung cancer development, particularly in select populations at risk of high or prolonged exposure. Hexavalent chromium [Cr(VI)] is a known carcinogen that is widely used in the manufacturing industry. While the link between Cr(VI) and lung cancer incidence is well‐accepted, the mechanisms through which Cr(VI) promotes lung cancer development are poorly understood. In the present study by Ge and colleagues published in Clinical and Translational Medicine, the authors explored the effects of prolonged Cr(VI) on non‐malignant lung epithelial cells. They determined that Cr(VI) initiates lung tumourigenesis by transforming a subpopulation of stem‐like, tumour initiating cells with increased expression of Aldehyde dehydrogenase 1 family member A1 (ALDH1A1). The observed increase in ALDH1A1 was dependent on transcriptional upregulation via Krüppel‐like factor 4 and associated with enhanced epidermal growth factor biosynthesis. Cr(VI)‐transformed tumour initiating cells accelerated tumour formation in vivo, which was ameliorated by therapeutic inhibition of ALDH1A1. Importantly, ALDH1A1 inhibition also sensitized Cr(VI)‐driven tumours to Gemcitabine chemotherapy and extended overall survival in mice. This study not only offers novel insight into the mechanisms through which Cr(VI) exposure initiates lung tumourigenesis but identifies a potential therapeutic target for patients with lung cancer secondary to Cr(VI) exposure. Additionally, this study underscores the importance of limiting exposure to Cr(VI) in the workplace and finding safer alternatives for use in the manufacturing industry.https://doi.org/10.1002/ctd2.155ALDH1A1cancer stem cellscarcinogensEGFhexavalent chromiumlung cancer |
| spellingShingle | Anastasia E. Metropulos Jeffrey H. Becker Daniel R. Principe Chromium (VI) promotes lung cancer initiation by activating EGF/ALDH1A1 signalling Clinical and Translational Discovery ALDH1A1 cancer stem cells carcinogens EGF hexavalent chromium lung cancer |
| title | Chromium (VI) promotes lung cancer initiation by activating EGF/ALDH1A1 signalling |
| title_full | Chromium (VI) promotes lung cancer initiation by activating EGF/ALDH1A1 signalling |
| title_fullStr | Chromium (VI) promotes lung cancer initiation by activating EGF/ALDH1A1 signalling |
| title_full_unstemmed | Chromium (VI) promotes lung cancer initiation by activating EGF/ALDH1A1 signalling |
| title_short | Chromium (VI) promotes lung cancer initiation by activating EGF/ALDH1A1 signalling |
| title_sort | chromium vi promotes lung cancer initiation by activating egf aldh1a1 signalling |
| topic | ALDH1A1 cancer stem cells carcinogens EGF hexavalent chromium lung cancer |
| url | https://doi.org/10.1002/ctd2.155 |
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