CBP-mediated Wnt3a/β-catenin signaling promotes cervical oncogenesis initiated by Piwil2
Our previous work demonstrated that Piwil2 reactivated by the human papillomavirus oncoproteins E6 and E7 may reprogram somatic cells into tumor-initiating cells (TICs), which contribute to cervical neoplasia lesions. Maintaining the stemness of TICs is critical for the progression of cervical lesio...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558620301688 |
| _version_ | 1819295842356428800 |
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| author | Dingqing Feng Keqin Yan Haiyan Liang Jing Liang Wenhui Wang Huan Yu Ying Zhou Weidong Zhao Zhongjun Dong Bin Ling |
| author_facet | Dingqing Feng Keqin Yan Haiyan Liang Jing Liang Wenhui Wang Huan Yu Ying Zhou Weidong Zhao Zhongjun Dong Bin Ling |
| author_sort | Dingqing Feng |
| collection | DOAJ |
| description | Our previous work demonstrated that Piwil2 reactivated by the human papillomavirus oncoproteins E6 and E7 may reprogram somatic cells into tumor-initiating cells (TICs), which contribute to cervical neoplasia lesions. Maintaining the stemness of TICs is critical for the progression of cervical lesions. Here, we determined that canonical Wnt signaling was aberrantly activated in HaCaT cells transfected with lentivirus expressing Piwil2 and in cervical lesion specimens of low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, and invasive carcinoma. Blocking the β-catenin and CREB binding protein interaction with ICG-001 significantly downregulated the reprogramming factors c-Myc, Nanog, Oct4, Sox2, and Klf4, thus leading to cell differentiation and preventing tumorigenicity in Piwil2-overexpressing HaCaT cells. Similarly, Piwil2 also critically regulated the canonical Wnt signaling pathway in cervical cancer. We further demonstrated that ICG-001 increased cisplatin sensitivity and significantly suppressed tumor growth of cervical cancer alone or in combination with cisplatin both in vitro and in vivo. The β-catenin/ CREB binding protein-mediated transcription activated by Piwil2 is essential for the maintenance of TICs, therefore contributing to the progression of cervical oncogenesis. |
| first_indexed | 2024-12-24T04:48:38Z |
| format | Article |
| id | doaj.art-4e0581fbfee34af39ca8d2460aa17836 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 |
| language | English |
| last_indexed | 2024-12-24T04:48:38Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-4e0581fbfee34af39ca8d2460aa178362022-12-21T17:14:36ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862021-01-01231111CBP-mediated Wnt3a/β-catenin signaling promotes cervical oncogenesis initiated by Piwil2Dingqing Feng0Keqin Yan1Haiyan Liang2Jing Liang3Wenhui Wang4Huan Yu5Ying Zhou6Weidong Zhao7Zhongjun Dong8Bin Ling9Department of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, China; Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaDepartment of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Obstetrics and Gynecology, the First Affiliated Hospital of University of Science and Technology of China, Hefei, ChinaDepartment of Gynecology and Oncology, Anhui Provincial Cancer Hospital, Hefei, ChinaSchool of Medicine, Tsinghua University, Beijing, ChinaDepartment of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, China; Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Corresponding author.Our previous work demonstrated that Piwil2 reactivated by the human papillomavirus oncoproteins E6 and E7 may reprogram somatic cells into tumor-initiating cells (TICs), which contribute to cervical neoplasia lesions. Maintaining the stemness of TICs is critical for the progression of cervical lesions. Here, we determined that canonical Wnt signaling was aberrantly activated in HaCaT cells transfected with lentivirus expressing Piwil2 and in cervical lesion specimens of low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, and invasive carcinoma. Blocking the β-catenin and CREB binding protein interaction with ICG-001 significantly downregulated the reprogramming factors c-Myc, Nanog, Oct4, Sox2, and Klf4, thus leading to cell differentiation and preventing tumorigenicity in Piwil2-overexpressing HaCaT cells. Similarly, Piwil2 also critically regulated the canonical Wnt signaling pathway in cervical cancer. We further demonstrated that ICG-001 increased cisplatin sensitivity and significantly suppressed tumor growth of cervical cancer alone or in combination with cisplatin both in vitro and in vivo. The β-catenin/ CREB binding protein-mediated transcription activated by Piwil2 is essential for the maintenance of TICs, therefore contributing to the progression of cervical oncogenesis.http://www.sciencedirect.com/science/article/pii/S1476558620301688Cervical cancerPiwil2Wnt signalingTumor initiating cellCBP |
| spellingShingle | Dingqing Feng Keqin Yan Haiyan Liang Jing Liang Wenhui Wang Huan Yu Ying Zhou Weidong Zhao Zhongjun Dong Bin Ling CBP-mediated Wnt3a/β-catenin signaling promotes cervical oncogenesis initiated by Piwil2 Neoplasia: An International Journal for Oncology Research Cervical cancer Piwil2 Wnt signaling Tumor initiating cell CBP |
| title | CBP-mediated Wnt3a/β-catenin signaling promotes cervical oncogenesis initiated by Piwil2 |
| title_full | CBP-mediated Wnt3a/β-catenin signaling promotes cervical oncogenesis initiated by Piwil2 |
| title_fullStr | CBP-mediated Wnt3a/β-catenin signaling promotes cervical oncogenesis initiated by Piwil2 |
| title_full_unstemmed | CBP-mediated Wnt3a/β-catenin signaling promotes cervical oncogenesis initiated by Piwil2 |
| title_short | CBP-mediated Wnt3a/β-catenin signaling promotes cervical oncogenesis initiated by Piwil2 |
| title_sort | cbp mediated wnt3a β catenin signaling promotes cervical oncogenesis initiated by piwil2 |
| topic | Cervical cancer Piwil2 Wnt signaling Tumor initiating cell CBP |
| url | http://www.sciencedirect.com/science/article/pii/S1476558620301688 |
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