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- Publisher Website: 10.1016/j.ygyno.2018.10.039
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Article: TROP-2 exhibits tumor suppressive functions in cervical cancer by dual inhibition of IGF-1R and ALK signaling
Title | TROP-2 exhibits tumor suppressive functions in cervical cancer by dual inhibition of IGF-1R and ALK signaling |
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Authors | |
Keywords | ALK Cervical cancerI GF-1R TROP-2 Tumor suppressor |
Issue Date | 2019 |
Publisher | Academic Press. The Journal's web site is located at http://www.elsevier.com/locate/ygyno |
Citation | Gynecologic Oncology, 2019, v. 152 n. 1, p. 185-193 How to Cite? |
Abstract | Objective: Inactivation of tumor suppressor genes promotes initiation and progression of cervical cancer. This study aims to investigate the tumor suppressive effects of TROP-2 in cervical cancer cells and to explain the underlying mechanisms. Methods: The tumor suppressive functions of TROP-2 in cervical cancer cells were examined by in vitro and in vivo tumorigenic functional assays. Downstream factors of TROP-2 were screened using Human Phospho-Receptor Tyrosine Kinase Array. Small molecule inhibitors were applied to HeLa cells to test the TROP-2 effects on the oncogenicity of IGF-1R and ALK. Protein interactions between TROP-2 and the ligands of IGF-1R and ALK were detected via immunoprecipitation assay and protein-protein affinity prediction. Results: In vitro and in vivo functional assays showed that overexpression of TROP-2 significantly inhibited the oncogenicity of cervical cancer cells; while knockdown of TROP-2 exhibited opposite effects. Human Phospho-Receptor Tyrosine Kinase Array showed that the activity of IGF-1R and ALK was stimulated by TROP-2 knockdown. Small molecule inhibitors AG1024 targeting IGF-1R and Crizotinib targeting ALK were treated to HeLa cells with and without TROP-2 overexpression, and results from cell viability and migration assays indicated that the oncogenicity of vector-transfected cells was repressed to a greater extent by the inhibition of either IGF-1R or ALK than that of the TROP-2-overexpressed cells. Immunoprecipitation assay and protein-protein affinity prediction suggested protein interactions between TROP-2 and the ligands of IGF-1R and ALK. Conclusions: Collectively, our results support that TROP-2 exhibits tumor suppressor functions in cervical cancer through inhibiting the activity of IGF-1R and ALK. © 2018 The Authors |
Persistent Identifier | http://hdl.handle.net/10722/276214 |
ISSN | 2023 Impact Factor: 4.5 2023 SCImago Journal Rankings: 1.627 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | SIN, TK | - |
dc.contributor.author | Li, Y | - |
dc.contributor.author | Liu, M | - |
dc.contributor.author | Ma, SKY | - |
dc.contributor.author | Guan, X | - |
dc.date.accessioned | 2019-09-10T02:58:18Z | - |
dc.date.available | 2019-09-10T02:58:18Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Gynecologic Oncology, 2019, v. 152 n. 1, p. 185-193 | - |
dc.identifier.issn | 0090-8258 | - |
dc.identifier.uri | http://hdl.handle.net/10722/276214 | - |
dc.description.abstract | Objective: Inactivation of tumor suppressor genes promotes initiation and progression of cervical cancer. This study aims to investigate the tumor suppressive effects of TROP-2 in cervical cancer cells and to explain the underlying mechanisms. Methods: The tumor suppressive functions of TROP-2 in cervical cancer cells were examined by in vitro and in vivo tumorigenic functional assays. Downstream factors of TROP-2 were screened using Human Phospho-Receptor Tyrosine Kinase Array. Small molecule inhibitors were applied to HeLa cells to test the TROP-2 effects on the oncogenicity of IGF-1R and ALK. Protein interactions between TROP-2 and the ligands of IGF-1R and ALK were detected via immunoprecipitation assay and protein-protein affinity prediction. Results: In vitro and in vivo functional assays showed that overexpression of TROP-2 significantly inhibited the oncogenicity of cervical cancer cells; while knockdown of TROP-2 exhibited opposite effects. Human Phospho-Receptor Tyrosine Kinase Array showed that the activity of IGF-1R and ALK was stimulated by TROP-2 knockdown. Small molecule inhibitors AG1024 targeting IGF-1R and Crizotinib targeting ALK were treated to HeLa cells with and without TROP-2 overexpression, and results from cell viability and migration assays indicated that the oncogenicity of vector-transfected cells was repressed to a greater extent by the inhibition of either IGF-1R or ALK than that of the TROP-2-overexpressed cells. Immunoprecipitation assay and protein-protein affinity prediction suggested protein interactions between TROP-2 and the ligands of IGF-1R and ALK. Conclusions: Collectively, our results support that TROP-2 exhibits tumor suppressor functions in cervical cancer through inhibiting the activity of IGF-1R and ALK. © 2018 The Authors | - |
dc.language | eng | - |
dc.publisher | Academic Press. The Journal's web site is located at http://www.elsevier.com/locate/ygyno | - |
dc.relation.ispartof | Gynecologic Oncology | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | ALK | - |
dc.subject | Cervical cancerI | - |
dc.subject | GF-1R | - |
dc.subject | TROP-2 | - |
dc.subject | Tumor suppressor | - |
dc.title | TROP-2 exhibits tumor suppressive functions in cervical cancer by dual inhibition of IGF-1R and ALK signaling | - |
dc.type | Article | - |
dc.identifier.email | Ma, SKY: stefma@hku.hk | - |
dc.identifier.email | Guan, X: xyguan@hku.hk | - |
dc.identifier.authority | Ma, SKY=rp00506 | - |
dc.identifier.authority | Guan, X=rp00454 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1016/j.ygyno.2018.10.039 | - |
dc.identifier.pmid | 30429055 | - |
dc.identifier.scopus | eid_2-s2.0-85056336349 | - |
dc.identifier.hkuros | 302590 | - |
dc.identifier.volume | 152 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | 185 | - |
dc.identifier.epage | 193 | - |
dc.identifier.isi | WOS:000456637000029 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 0090-8258 | - |