ISG15 Promotes ERK1 ISGylation, CD8+ T Cell Activation and Suppresses Ovarian Cancer Progression
Increased number of tumor-infiltrating CD8+ lymphocytes is associated with improved survival in patients with advanced stage high grade serous ovarian cancer (HGSOC) but the underlying molecular mechanism has not been thoroughly explored. Using transcriptome profiling of microdissected HGSOC tissue...
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doaj-7ed93127be2f43bf918e5d32ebd5f6662020-11-25T00:40:27ZengMDPI AGCancers2072-66942018-11-01101246410.3390/cancers10120464cancers10120464ISG15 Promotes ERK1 ISGylation, CD8+ T Cell Activation and Suppresses Ovarian Cancer ProgressionTsz-Lun Yeung0Ching Chou Tsai1Cecilia S. Leung2Chi-Lam Au Yeung3Melissa S. Thompson4Karen H. Lu5Ralph S. Freedman6Michael J. Birrer7Kwong-Kwok Wong8Samuel C. Mok9Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAComprehensive Cancer Center, Division of Hematology-Oncology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAIncreased number of tumor-infiltrating CD8+ lymphocytes is associated with improved survival in patients with advanced stage high grade serous ovarian cancer (HGSOC) but the underlying molecular mechanism has not been thoroughly explored. Using transcriptome profiling of microdissected HGSOC tissue with high and low CD8+ lymphocyte count and subsequent validation studies, we demonstrated that significantly increased ISG15 (Interferon-stimulated gene 15) expression in HGSOC was associated with high CD8+ lymphocyte count and with the improvement in median overall survival in both univariate and multivariate analyses. Further functional studies showed that endogenous and exogenous ISG15 suppressed ovarian cancer progression through ISGylation of ERK in HGSOC, and activation of NK cells and CD8+ T lymphocytes. These data suggest that the development of treatment strategies based on up-regulating ISG15 in ovarian cancer cells or increased circulating ISG15 in ovarian cancer patients is warranted.https://www.mdpi.com/2072-6694/10/12/464ovarian cancerISG15CD8+ lymphocyteinterferonISGylation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tsz-Lun Yeung Ching Chou Tsai Cecilia S. Leung Chi-Lam Au Yeung Melissa S. Thompson Karen H. Lu Ralph S. Freedman Michael J. Birrer Kwong-Kwok Wong Samuel C. Mok |
spellingShingle |
Tsz-Lun Yeung Ching Chou Tsai Cecilia S. Leung Chi-Lam Au Yeung Melissa S. Thompson Karen H. Lu Ralph S. Freedman Michael J. Birrer Kwong-Kwok Wong Samuel C. Mok ISG15 Promotes ERK1 ISGylation, CD8+ T Cell Activation and Suppresses Ovarian Cancer Progression Cancers ovarian cancer ISG15 CD8+ lymphocyte interferon ISGylation |
author_facet |
Tsz-Lun Yeung Ching Chou Tsai Cecilia S. Leung Chi-Lam Au Yeung Melissa S. Thompson Karen H. Lu Ralph S. Freedman Michael J. Birrer Kwong-Kwok Wong Samuel C. Mok |
author_sort |
Tsz-Lun Yeung |
title |
ISG15 Promotes ERK1 ISGylation, CD8+ T Cell Activation and Suppresses Ovarian Cancer Progression |
title_short |
ISG15 Promotes ERK1 ISGylation, CD8+ T Cell Activation and Suppresses Ovarian Cancer Progression |
title_full |
ISG15 Promotes ERK1 ISGylation, CD8+ T Cell Activation and Suppresses Ovarian Cancer Progression |
title_fullStr |
ISG15 Promotes ERK1 ISGylation, CD8+ T Cell Activation and Suppresses Ovarian Cancer Progression |
title_full_unstemmed |
ISG15 Promotes ERK1 ISGylation, CD8+ T Cell Activation and Suppresses Ovarian Cancer Progression |
title_sort |
isg15 promotes erk1 isgylation, cd8+ t cell activation and suppresses ovarian cancer progression |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2018-11-01 |
description |
Increased number of tumor-infiltrating CD8+ lymphocytes is associated with improved survival in patients with advanced stage high grade serous ovarian cancer (HGSOC) but the underlying molecular mechanism has not been thoroughly explored. Using transcriptome profiling of microdissected HGSOC tissue with high and low CD8+ lymphocyte count and subsequent validation studies, we demonstrated that significantly increased ISG15 (Interferon-stimulated gene 15) expression in HGSOC was associated with high CD8+ lymphocyte count and with the improvement in median overall survival in both univariate and multivariate analyses. Further functional studies showed that endogenous and exogenous ISG15 suppressed ovarian cancer progression through ISGylation of ERK in HGSOC, and activation of NK cells and CD8+ T lymphocytes. These data suggest that the development of treatment strategies based on up-regulating ISG15 in ovarian cancer cells or increased circulating ISG15 in ovarian cancer patients is warranted. |
topic |
ovarian cancer ISG15 CD8+ lymphocyte interferon ISGylation |
url |
https://www.mdpi.com/2072-6694/10/12/464 |
work_keys_str_mv |
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