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Article: TROP-2 exhibits tumor suppressive functions in cervical cancer by dual inhibition of IGF-1R and ALK signaling

TitleTROP-2 exhibits tumor suppressive functions in cervical cancer by dual inhibition of IGF-1R and ALK signaling
Authors
KeywordsALK
Cervical cancerI
GF-1R
TROP-2
Tumor suppressor
Issue Date2019
PublisherAcademic 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?
AbstractObjective: 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 Identifierhttp://hdl.handle.net/10722/276214
ISSN
2019 Impact Factor: 4.623
2015 SCImago Journal Rankings: 2.284
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSIN, TK-
dc.contributor.authorLi, Y-
dc.contributor.authorLiu, M-
dc.contributor.authorMa, SKY-
dc.contributor.authorGuan, X-
dc.date.accessioned2019-09-10T02:58:18Z-
dc.date.available2019-09-10T02:58:18Z-
dc.date.issued2019-
dc.identifier.citationGynecologic Oncology, 2019, v. 152 n. 1, p. 185-193-
dc.identifier.issn0090-8258-
dc.identifier.urihttp://hdl.handle.net/10722/276214-
dc.description.abstractObjective: 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.languageeng-
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ygyno-
dc.relation.ispartofGynecologic Oncology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectALK-
dc.subjectCervical cancerI-
dc.subjectGF-1R-
dc.subjectTROP-2-
dc.subjectTumor suppressor-
dc.titleTROP-2 exhibits tumor suppressive functions in cervical cancer by dual inhibition of IGF-1R and ALK signaling-
dc.typeArticle-
dc.identifier.emailMa, SKY: stefma@hku.hk-
dc.identifier.emailGuan, X: xyguan@hku.hk-
dc.identifier.authorityMa, SKY=rp00506-
dc.identifier.authorityGuan, X=rp00454-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.ygyno.2018.10.039-
dc.identifier.pmid30429055-
dc.identifier.scopuseid_2-s2.0-85056336349-
dc.identifier.hkuros302590-
dc.identifier.volume152-
dc.identifier.issue1-
dc.identifier.spage185-
dc.identifier.epage193-
dc.identifier.isiWOS:000456637000029-
dc.publisher.placeUnited States-

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