STAT3/PIAS3 Levels Serve as “Early Signature” Genes in the Development of High-Grade Serous Carcinoma from the Fallopian Tube

Publication Date:
2018-04-03
Publisher:
The American Association for Cancer Research (AACR)
Print ISSN:
0008-5472
Electronic ISSN:
1538-7445
Topics:
Medicine
Published by:
http://www.aacr.org/
_version_ 1836398874722304000
autor Uksha Saini, Adrian A. Suarez, Shan Naidu, John J. Wallbillich, Kristin Bixel, Ross A. Wanner, Jason Bice, Raleigh D. Kladney, Jenny Lester, Beth Y. Karlan, Paul J. Goodfellow, David E. Cohn, Karuppaiyah Selvendiran
beschreibung The initial molecular events that lead to malignant transformation of the fimbria of the fallopian tube (FT) through high-grade serous ovarian carcinoma (HGSC) remain poorly understood. In this study, we report that increased expression of signal transducer and activator of transcription 3 (pSTAT3 Tyr705) and suppression or loss of protein inhibitor of activated STAT3 (PIAS3) in FT likely drive HGSC. We evaluated human tissues-benign normal FT, tubal-peritoneal junction (TPJ), p53 signature FT tissue, tubal intraepithelial lesion in transition (TILT), serous tubal intraepithelial carcinoma (STIC) without ovarian cancer, and HGSC for expression of STAT3/PIAS3 (compared with their known TP53 signature) and their target proliferation genes. We observed constitutive activation of STAT3 and low levels or loss of PIAS3 in the TPJ, p53 signature, TILT, and STIC through advanced stage IV (HGSC) tissues. Elevated expression of pSTAT3 Tyr705 and decreased levels of PIAS3 appeared as early as TPJ and the trend continued until very advanced stage HGSC (compared with high PIAS3 and low pSTAT3 expression in normal benign FT). Exogenous expression of STAT3 in FT cells mediated translocation of pSTAT3 and c-Myc into the nucleus. In vivo experiments demonstrated that overexpression of STAT3 in FT secretory epithelial cells promoted tumor progression and metastasis, mimicking the clinical disease observed in patients with HGSC. Thus, we conclude that the STAT3 pathway plays a role in the development and progression of HGSC from its earliest premalignant states.Significance: Concomitant gain of pSTAT3 Tyr705 and loss of PIAS3 appear critical for initiation and development of high-grade serous carcinoma. Cancer Res; 78(7); 1739–50. ©2018 AACR.
citation_standardnr 6223991
datenlieferant ipn_articles
feed_id 9360
feed_publisher The American Association for Cancer Research (AACR)
feed_publisher_url http://www.aacr.org/
insertion_date 2018-04-03
journaleissn 1538-7445
journalissn 0008-5472
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Association for Cancer Research (AACR)
quelle Cancer Research
relation http://cancerres.aacrjournals.org/content/78/7/1739.short?rss=1
search_space articles
shingle_author_1 Uksha Saini, Adrian A. Suarez, Shan Naidu, John J. Wallbillich, Kristin Bixel, Ross A. Wanner, Jason Bice, Raleigh D. Kladney, Jenny Lester, Beth Y. Karlan, Paul J. Goodfellow, David E. Cohn, Karuppaiyah Selvendiran
shingle_author_2 Uksha Saini, Adrian A. Suarez, Shan Naidu, John J. Wallbillich, Kristin Bixel, Ross A. Wanner, Jason Bice, Raleigh D. Kladney, Jenny Lester, Beth Y. Karlan, Paul J. Goodfellow, David E. Cohn, Karuppaiyah Selvendiran
shingle_author_3 Uksha Saini, Adrian A. Suarez, Shan Naidu, John J. Wallbillich, Kristin Bixel, Ross A. Wanner, Jason Bice, Raleigh D. Kladney, Jenny Lester, Beth Y. Karlan, Paul J. Goodfellow, David E. Cohn, Karuppaiyah Selvendiran
shingle_author_4 Uksha Saini, Adrian A. Suarez, Shan Naidu, John J. Wallbillich, Kristin Bixel, Ross A. Wanner, Jason Bice, Raleigh D. Kladney, Jenny Lester, Beth Y. Karlan, Paul J. Goodfellow, David E. Cohn, Karuppaiyah Selvendiran
shingle_catch_all_1 STAT3/PIAS3 Levels Serve as “Early Signature” Genes in the Development of High-Grade Serous Carcinoma from the Fallopian Tube
The initial molecular events that lead to malignant transformation of the fimbria of the fallopian tube (FT) through high-grade serous ovarian carcinoma (HGSC) remain poorly understood. In this study, we report that increased expression of signal transducer and activator of transcription 3 (pSTAT3 Tyr705) and suppression or loss of protein inhibitor of activated STAT3 (PIAS3) in FT likely drive HGSC. We evaluated human tissues-benign normal FT, tubal-peritoneal junction (TPJ), p53 signature FT tissue, tubal intraepithelial lesion in transition (TILT), serous tubal intraepithelial carcinoma (STIC) without ovarian cancer, and HGSC for expression of STAT3/PIAS3 (compared with their known TP53 signature) and their target proliferation genes. We observed constitutive activation of STAT3 and low levels or loss of PIAS3 in the TPJ, p53 signature, TILT, and STIC through advanced stage IV (HGSC) tissues. Elevated expression of pSTAT3 Tyr705 and decreased levels of PIAS3 appeared as early as TPJ and the trend continued until very advanced stage HGSC (compared with high PIAS3 and low pSTAT3 expression in normal benign FT). Exogenous expression of STAT3 in FT cells mediated translocation of pSTAT3 and c-Myc into the nucleus. In vivo experiments demonstrated that overexpression of STAT3 in FT secretory epithelial cells promoted tumor progression and metastasis, mimicking the clinical disease observed in patients with HGSC. Thus, we conclude that the STAT3 pathway plays a role in the development and progression of HGSC from its earliest premalignant states.Significance: Concomitant gain of pSTAT3 Tyr705 and loss of PIAS3 appear critical for initiation and development of high-grade serous carcinoma. Cancer Res; 78(7); 1739–50. ©2018 AACR.
Uksha Saini, Adrian A. Suarez, Shan Naidu, John J. Wallbillich, Kristin Bixel, Ross A. Wanner, Jason Bice, Raleigh D. Kladney, Jenny Lester, Beth Y. Karlan, Paul J. Goodfellow, David E. Cohn, Karuppaiyah Selvendiran
The American Association for Cancer Research (AACR)
0008-5472
00085472
1538-7445
15387445
shingle_catch_all_2 STAT3/PIAS3 Levels Serve as “Early Signature” Genes in the Development of High-Grade Serous Carcinoma from the Fallopian Tube
The initial molecular events that lead to malignant transformation of the fimbria of the fallopian tube (FT) through high-grade serous ovarian carcinoma (HGSC) remain poorly understood. In this study, we report that increased expression of signal transducer and activator of transcription 3 (pSTAT3 Tyr705) and suppression or loss of protein inhibitor of activated STAT3 (PIAS3) in FT likely drive HGSC. We evaluated human tissues-benign normal FT, tubal-peritoneal junction (TPJ), p53 signature FT tissue, tubal intraepithelial lesion in transition (TILT), serous tubal intraepithelial carcinoma (STIC) without ovarian cancer, and HGSC for expression of STAT3/PIAS3 (compared with their known TP53 signature) and their target proliferation genes. We observed constitutive activation of STAT3 and low levels or loss of PIAS3 in the TPJ, p53 signature, TILT, and STIC through advanced stage IV (HGSC) tissues. Elevated expression of pSTAT3 Tyr705 and decreased levels of PIAS3 appeared as early as TPJ and the trend continued until very advanced stage HGSC (compared with high PIAS3 and low pSTAT3 expression in normal benign FT). Exogenous expression of STAT3 in FT cells mediated translocation of pSTAT3 and c-Myc into the nucleus. In vivo experiments demonstrated that overexpression of STAT3 in FT secretory epithelial cells promoted tumor progression and metastasis, mimicking the clinical disease observed in patients with HGSC. Thus, we conclude that the STAT3 pathway plays a role in the development and progression of HGSC from its earliest premalignant states.Significance: Concomitant gain of pSTAT3 Tyr705 and loss of PIAS3 appear critical for initiation and development of high-grade serous carcinoma. Cancer Res; 78(7); 1739–50. ©2018 AACR.
Uksha Saini, Adrian A. Suarez, Shan Naidu, John J. Wallbillich, Kristin Bixel, Ross A. Wanner, Jason Bice, Raleigh D. Kladney, Jenny Lester, Beth Y. Karlan, Paul J. Goodfellow, David E. Cohn, Karuppaiyah Selvendiran
The American Association for Cancer Research (AACR)
0008-5472
00085472
1538-7445
15387445
shingle_catch_all_3 STAT3/PIAS3 Levels Serve as “Early Signature” Genes in the Development of High-Grade Serous Carcinoma from the Fallopian Tube
The initial molecular events that lead to malignant transformation of the fimbria of the fallopian tube (FT) through high-grade serous ovarian carcinoma (HGSC) remain poorly understood. In this study, we report that increased expression of signal transducer and activator of transcription 3 (pSTAT3 Tyr705) and suppression or loss of protein inhibitor of activated STAT3 (PIAS3) in FT likely drive HGSC. We evaluated human tissues-benign normal FT, tubal-peritoneal junction (TPJ), p53 signature FT tissue, tubal intraepithelial lesion in transition (TILT), serous tubal intraepithelial carcinoma (STIC) without ovarian cancer, and HGSC for expression of STAT3/PIAS3 (compared with their known TP53 signature) and their target proliferation genes. We observed constitutive activation of STAT3 and low levels or loss of PIAS3 in the TPJ, p53 signature, TILT, and STIC through advanced stage IV (HGSC) tissues. Elevated expression of pSTAT3 Tyr705 and decreased levels of PIAS3 appeared as early as TPJ and the trend continued until very advanced stage HGSC (compared with high PIAS3 and low pSTAT3 expression in normal benign FT). Exogenous expression of STAT3 in FT cells mediated translocation of pSTAT3 and c-Myc into the nucleus. In vivo experiments demonstrated that overexpression of STAT3 in FT secretory epithelial cells promoted tumor progression and metastasis, mimicking the clinical disease observed in patients with HGSC. Thus, we conclude that the STAT3 pathway plays a role in the development and progression of HGSC from its earliest premalignant states.Significance: Concomitant gain of pSTAT3 Tyr705 and loss of PIAS3 appear critical for initiation and development of high-grade serous carcinoma. Cancer Res; 78(7); 1739–50. ©2018 AACR.
Uksha Saini, Adrian A. Suarez, Shan Naidu, John J. Wallbillich, Kristin Bixel, Ross A. Wanner, Jason Bice, Raleigh D. Kladney, Jenny Lester, Beth Y. Karlan, Paul J. Goodfellow, David E. Cohn, Karuppaiyah Selvendiran
The American Association for Cancer Research (AACR)
0008-5472
00085472
1538-7445
15387445
shingle_catch_all_4 STAT3/PIAS3 Levels Serve as “Early Signature” Genes in the Development of High-Grade Serous Carcinoma from the Fallopian Tube
The initial molecular events that lead to malignant transformation of the fimbria of the fallopian tube (FT) through high-grade serous ovarian carcinoma (HGSC) remain poorly understood. In this study, we report that increased expression of signal transducer and activator of transcription 3 (pSTAT3 Tyr705) and suppression or loss of protein inhibitor of activated STAT3 (PIAS3) in FT likely drive HGSC. We evaluated human tissues-benign normal FT, tubal-peritoneal junction (TPJ), p53 signature FT tissue, tubal intraepithelial lesion in transition (TILT), serous tubal intraepithelial carcinoma (STIC) without ovarian cancer, and HGSC for expression of STAT3/PIAS3 (compared with their known TP53 signature) and their target proliferation genes. We observed constitutive activation of STAT3 and low levels or loss of PIAS3 in the TPJ, p53 signature, TILT, and STIC through advanced stage IV (HGSC) tissues. Elevated expression of pSTAT3 Tyr705 and decreased levels of PIAS3 appeared as early as TPJ and the trend continued until very advanced stage HGSC (compared with high PIAS3 and low pSTAT3 expression in normal benign FT). Exogenous expression of STAT3 in FT cells mediated translocation of pSTAT3 and c-Myc into the nucleus. In vivo experiments demonstrated that overexpression of STAT3 in FT secretory epithelial cells promoted tumor progression and metastasis, mimicking the clinical disease observed in patients with HGSC. Thus, we conclude that the STAT3 pathway plays a role in the development and progression of HGSC from its earliest premalignant states.Significance: Concomitant gain of pSTAT3 Tyr705 and loss of PIAS3 appear critical for initiation and development of high-grade serous carcinoma. Cancer Res; 78(7); 1739–50. ©2018 AACR.
Uksha Saini, Adrian A. Suarez, Shan Naidu, John J. Wallbillich, Kristin Bixel, Ross A. Wanner, Jason Bice, Raleigh D. Kladney, Jenny Lester, Beth Y. Karlan, Paul J. Goodfellow, David E. Cohn, Karuppaiyah Selvendiran
The American Association for Cancer Research (AACR)
0008-5472
00085472
1538-7445
15387445
shingle_title_1 STAT3/PIAS3 Levels Serve as “Early Signature” Genes in the Development of High-Grade Serous Carcinoma from the Fallopian Tube
shingle_title_2 STAT3/PIAS3 Levels Serve as “Early Signature” Genes in the Development of High-Grade Serous Carcinoma from the Fallopian Tube
shingle_title_3 STAT3/PIAS3 Levels Serve as “Early Signature” Genes in the Development of High-Grade Serous Carcinoma from the Fallopian Tube
shingle_title_4 STAT3/PIAS3 Levels Serve as “Early Signature” Genes in the Development of High-Grade Serous Carcinoma from the Fallopian Tube
timestamp 2025-06-30T23:34:01.458Z
titel STAT3/PIAS3 Levels Serve as “Early Signature” Genes in the Development of High-Grade Serous Carcinoma from the Fallopian Tube
titel_suche STAT3/PIAS3 Levels Serve as “Early Signature” Genes in the Development of High-Grade Serous Carcinoma from the Fallopian Tube
topic WW-YZ
uid ipn_articles_6223991