ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion
Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-06-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/07270 |
| _version_ | 1797997494179725312 |
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| author | Wei-Ta Chen Nancy D Ebelt Travis H Stracker Blerta Xhemalce Carla L Van Den Berg Kyle M Miller |
| author_facet | Wei-Ta Chen Nancy D Ebelt Travis H Stracker Blerta Xhemalce Carla L Van Den Berg Kyle M Miller |
| author_sort | Wei-Ta Chen |
| collection | DOAJ |
| description | Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene network, including the chemokine IL-8, regulated by ATM. IL-8 expression required ATM and was regulated by oxidative stress. IL-8 was validated as an ATM target by its ability to rescue cell migration and invasion defects in ATM-depleted cells. Finally, ATM-depletion in human breast cancer cells reduced lung tumors in a mouse xenograft model and clinical data validated IL-8 in lung metastasis. These findings provide insights into how ATM activation by oxidative stress regulates IL-8 to sustain cell migration and invasion in cancer cells to promote metastatic potential. Thus, in addition to well-established roles in tumor suppression, these findings identify a role for ATM in tumor progression. |
| first_indexed | 2024-04-11T10:33:53Z |
| format | Article |
| id | doaj.art-b022db6c1de84b82ba2b3a3238f5860f |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:33:53Z |
| publishDate | 2015-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-b022db6c1de84b82ba2b3a3238f5860f2022-12-22T04:29:21ZengeLife Sciences Publications LtdeLife2050-084X2015-06-01410.7554/eLife.07270ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasionWei-Ta Chen0Nancy D Ebelt1Travis H Stracker2Blerta Xhemalce3Carla L Van Den Berg4Kyle M Miller5Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, United StatesDepartment of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, United States; Division of Pharmacology and Toxicology, College of Pharmacy, Dell Pediatric Research Institute, University of Texas at Austin, Austin, United StatesOncology Programme, Institute for Research in Biomedicine, Barcelona, SpainDepartment of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, United StatesDepartment of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, United States; Division of Pharmacology and Toxicology, College of Pharmacy, Dell Pediatric Research Institute, University of Texas at Austin, Austin, United StatesDepartment of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, United StatesAtaxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene network, including the chemokine IL-8, regulated by ATM. IL-8 expression required ATM and was regulated by oxidative stress. IL-8 was validated as an ATM target by its ability to rescue cell migration and invasion defects in ATM-depleted cells. Finally, ATM-depletion in human breast cancer cells reduced lung tumors in a mouse xenograft model and clinical data validated IL-8 in lung metastasis. These findings provide insights into how ATM activation by oxidative stress regulates IL-8 to sustain cell migration and invasion in cancer cells to promote metastatic potential. Thus, in addition to well-established roles in tumor suppression, these findings identify a role for ATM in tumor progression.https://elifesciences.org/articles/07270DNA damageATMIL-8cell migrationROS |
| spellingShingle | Wei-Ta Chen Nancy D Ebelt Travis H Stracker Blerta Xhemalce Carla L Van Den Berg Kyle M Miller ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion eLife DNA damage ATM IL-8 cell migration ROS |
| title | ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion |
| title_full | ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion |
| title_fullStr | ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion |
| title_full_unstemmed | ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion |
| title_short | ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion |
| title_sort | atm regulation of il 8 links oxidative stress to cancer cell migration and invasion |
| topic | DNA damage ATM IL-8 cell migration ROS |
| url | https://elifesciences.org/articles/07270 |
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