File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)

Article: FSTL1 promotes metastasis and chemoresistance in esophageal squamous cell carcinoma through NFκB-BMP signaling cross-talk

TitleFSTL1 promotes metastasis and chemoresistance in esophageal squamous cell carcinoma through NFκB-BMP signaling cross-talk
Authors
Issue Date2017
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2017, v. 77 n. 21, p. 5886-5899 How to Cite?
AbstractEsophageal squamous cell carcinoma (ESCC) has a generally poor prognosis, and molecular markers to improve early detection and predict outcomes are greatly needed. Here, we report that the BMP-binding follistatin-like protein FSTL1 is overexpressed in ESCCs, where it correlates with poor overall survival. Genetic amplification of FSTL1 or chromosome 3q, where it is located, occurred frequently in ESCC, where FSTL1 copy number correlated positively with higher FSTL1 protein expression. Elevating FSTL1 levels by various means was sufficient to drive ESCC cell proliferation, clonogenicity, migration, invasion, self-renewal, and cisplatin resistance in vitro and tumorigenicity and distant metastasis in vivo. Conversely, FSTL1 attenuation by shRNA or neutralizing antibody elicited the opposite effects in ESCC cells. mRNA profiling analyses suggested that FSTL1 drives ESCC oncogenesis and metastasis through various pathways, with deregulation of NFκB and BMP signaling figuring prominently. Cross-talk between the NFκB and BMP pathways was evidenced by functional rescue experiments using inhibitors of NFκB and TLR4. Our results establish the significance of FSTL1 in driving oncogenesis and metastasis in ESCC by coordinating NFκB and BMP pathway control, with implications for its potential use as a diagnostic or prognostic biomarker and as a candidate therapeutic target in this disease setting.
Persistent Identifierhttp://hdl.handle.net/10722/244683
ISSN
2017 Impact Factor: 9.13
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLau, MCC-
dc.contributor.authorNg, KY-
dc.contributor.authorWong, TL-
dc.contributor.authorTong, M-
dc.contributor.authorLee, TK-
dc.contributor.authorMing, X-
dc.contributor.authorLaw, S-
dc.contributor.authorLee, NP-
dc.contributor.authorCheung, AL-
dc.contributor.authorQin, YR-
dc.contributor.authorChan, KW-
dc.contributor.authorNing, W-
dc.contributor.authorGuan, X-
dc.contributor.authorMa, S-
dc.date.accessioned2017-09-18T01:57:08Z-
dc.date.available2017-09-18T01:57:08Z-
dc.date.issued2017-
dc.identifier.citationCancer Research, 2017, v. 77 n. 21, p. 5886-5899-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/244683-
dc.description.abstractEsophageal squamous cell carcinoma (ESCC) has a generally poor prognosis, and molecular markers to improve early detection and predict outcomes are greatly needed. Here, we report that the BMP-binding follistatin-like protein FSTL1 is overexpressed in ESCCs, where it correlates with poor overall survival. Genetic amplification of FSTL1 or chromosome 3q, where it is located, occurred frequently in ESCC, where FSTL1 copy number correlated positively with higher FSTL1 protein expression. Elevating FSTL1 levels by various means was sufficient to drive ESCC cell proliferation, clonogenicity, migration, invasion, self-renewal, and cisplatin resistance in vitro and tumorigenicity and distant metastasis in vivo. Conversely, FSTL1 attenuation by shRNA or neutralizing antibody elicited the opposite effects in ESCC cells. mRNA profiling analyses suggested that FSTL1 drives ESCC oncogenesis and metastasis through various pathways, with deregulation of NFκB and BMP signaling figuring prominently. Cross-talk between the NFκB and BMP pathways was evidenced by functional rescue experiments using inhibitors of NFκB and TLR4. Our results establish the significance of FSTL1 in driving oncogenesis and metastasis in ESCC by coordinating NFκB and BMP pathway control, with implications for its potential use as a diagnostic or prognostic biomarker and as a candidate therapeutic target in this disease setting.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/-
dc.relation.ispartofCancer Research-
dc.titleFSTL1 promotes metastasis and chemoresistance in esophageal squamous cell carcinoma through NFκB-BMP signaling cross-talk-
dc.typeArticle-
dc.identifier.emailNg, KY: jkyng@hku.hk-
dc.identifier.emailWong, TL: tinlwong@hku.hk-
dc.identifier.emailTong, M: caroltm@hku.hk-
dc.identifier.emailLaw, S: slaw@hkucc.hku.hk-
dc.identifier.emailLee, NP: nikkilee@hku.hk-
dc.identifier.emailCheung, AL: lmcheung@hku.hk-
dc.identifier.emailChan, KW: kwchan@pathology.hku.hk-
dc.identifier.emailGuan, X: xyguan@hkucc.hku.hk-
dc.identifier.emailMa, S: stefma@hku.hk-
dc.identifier.authorityTong, M=rp02568-
dc.identifier.authorityLaw, S=rp00437-
dc.identifier.authorityLee, NP=rp00263-
dc.identifier.authorityCheung, AL=rp00332-
dc.identifier.authorityChan, KW=rp00330-
dc.identifier.authorityGuan, X=rp00454-
dc.identifier.authorityMa, S=rp00506-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/0008-5472.CAN-17-1411-
dc.identifier.pmid28883005-
dc.identifier.scopuseid_2-s2.0-85035009074-
dc.identifier.hkuros278407-
dc.identifier.volume77-
dc.identifier.issue21-
dc.identifier.spage5886-
dc.identifier.epage5899-
dc.identifier.isiWOS:000414248300049-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats