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Article: Novel Nuclear Partnering Role of EPS8 With FOXM1 in Regulating Cell Proliferation

TitleNovel Nuclear Partnering Role of EPS8 With FOXM1 in Regulating Cell Proliferation
Authors
KeywordsCCNB1
Cell proliferation
EPS8
FOXM1
Nuclear export signal
Issue Date2019
PublisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/oncology
Citation
Frontiers in Oncology, 2019, v. 9, article no. 154 How to Cite?
AbstractOne hallmark of cancer cells is sustaining proliferative signaling that leads to uncontrolled cell proliferation. Both the Forkhead box (FOX) M1 transcription factor and the Epidermal Growth Factor (EGF) receptor Pathway Substrate 8 (EPS8) are known to be activated by mitogenic signaling and their levels upregulated in cancer. Well-known to regulate Rac-mediated actin remodeling at the cell cortex, EPS8 carries a nuclear localization signal but its possible nuclear role remains unclear. Here, we demonstrated interaction of FOXM1 with EPS8 in yeast two-hybrid and immunoprecipitation assays. Immunostaining revealed co-localization of the two proteins during G2/M phase of the cell cycle. EPS8 became nuclear localized when CRM1/Exportin 1-dependent nuclear export was inhibited by Leptomycin B, and a functional nuclear export signal could be identified within EPS8 using EGFP-tagging and site-directed mutagenesis. Downregulation of EPS8 using shRNAs suppressed expression of FOXM1 and the FOXM1-target CCNB1, and slowed down G2/M transition in cervical cancer cells. Chromatin immunoprecipitation analysis indicated recruitment of EPS8 to the CCNB1 and CDC25B promoters. Taken together, our findings support a novel partnering role of EPS8 with FOXM1 in the regulation of cancer cell proliferation and provides interesting insight into future design of therapeutic strategy to inhibit cancer cell proliferation.
Persistent Identifierhttp://hdl.handle.net/10722/271921
ISSN
2019 Impact Factor: 4.848
2015 SCImago Journal Rankings: 2.133
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorNgan, AWL-
dc.contributor.authorTsui, MG-
dc.contributor.authorSo, HF-
dc.contributor.authorLeung, WY-
dc.contributor.authorChan, DW-
dc.contributor.authorYao, KM-
dc.date.accessioned2019-07-20T10:32:08Z-
dc.date.available2019-07-20T10:32:08Z-
dc.date.issued2019-
dc.identifier.citationFrontiers in Oncology, 2019, v. 9, article no. 154-
dc.identifier.issn2234-943X-
dc.identifier.urihttp://hdl.handle.net/10722/271921-
dc.description.abstractOne hallmark of cancer cells is sustaining proliferative signaling that leads to uncontrolled cell proliferation. Both the Forkhead box (FOX) M1 transcription factor and the Epidermal Growth Factor (EGF) receptor Pathway Substrate 8 (EPS8) are known to be activated by mitogenic signaling and their levels upregulated in cancer. Well-known to regulate Rac-mediated actin remodeling at the cell cortex, EPS8 carries a nuclear localization signal but its possible nuclear role remains unclear. Here, we demonstrated interaction of FOXM1 with EPS8 in yeast two-hybrid and immunoprecipitation assays. Immunostaining revealed co-localization of the two proteins during G2/M phase of the cell cycle. EPS8 became nuclear localized when CRM1/Exportin 1-dependent nuclear export was inhibited by Leptomycin B, and a functional nuclear export signal could be identified within EPS8 using EGFP-tagging and site-directed mutagenesis. Downregulation of EPS8 using shRNAs suppressed expression of FOXM1 and the FOXM1-target CCNB1, and slowed down G2/M transition in cervical cancer cells. Chromatin immunoprecipitation analysis indicated recruitment of EPS8 to the CCNB1 and CDC25B promoters. Taken together, our findings support a novel partnering role of EPS8 with FOXM1 in the regulation of cancer cell proliferation and provides interesting insight into future design of therapeutic strategy to inhibit cancer cell proliferation.-
dc.languageeng-
dc.publisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/oncology-
dc.relation.ispartofFrontiers in Oncology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCCNB1-
dc.subjectCell proliferation-
dc.subjectEPS8-
dc.subjectFOXM1-
dc.subjectNuclear export signal-
dc.titleNovel Nuclear Partnering Role of EPS8 With FOXM1 in Regulating Cell Proliferation-
dc.typeArticle-
dc.identifier.emailTsui, MG: mtsui@hku.hk-
dc.identifier.emailLeung, WY: gwyleung@hku.hk-
dc.identifier.emailChan, DW: dwchan@hku.hk-
dc.identifier.emailYao, KM: kmyao@hku.hk-
dc.identifier.authorityChan, DW=rp00543-
dc.identifier.authorityYao, KM=rp00344-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3389/fonc.2019.00154-
dc.identifier.pmid30941306-
dc.identifier.pmcidPMC6433973-
dc.identifier.scopuseid_2-s2.0-85063319041-
dc.identifier.hkuros298772-
dc.identifier.volume9-
dc.identifier.spagearticle no. 154-
dc.identifier.epagearticle no. 154-
dc.identifier.isiWOS:000461651300004-
dc.publisher.placeSwitzerland-
dc.identifier.issnl2234-943X-

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