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Article: Mechanisms through which hypoxia-induced caveolin-1 drives tumorigenesis and metastasis in hepatocellular carcinoma

TitleMechanisms through which hypoxia-induced caveolin-1 drives tumorigenesis and metastasis in hepatocellular carcinoma
Authors
Issue Date2016
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2016, v. 76 n. 24, p. 7242-7253 How to Cite?
AbstractIn solid tumors, hypoxia triggers an aberrant vasculogenesis, enhances malignant character, and elevates metastatic risk. The plasma membrane organizing protein caveolin-1 (Cav1) is increased in a variety of cancers, including hepatocellular carcinoma (HCC), where it contributes to metastatic capability. However, the reason for elevation of Cav1 in tumor cells and the mechanistic basis for its contributions to metastatic risk are not fully understood. Here, we show that in HCC cells, hypoxia elevates expression of Cav1, which then acts through the calcium-binding protein S100P to promote metastasis. Hypoxic regions of HCC xenografts displayed elevated expression of Cav1. Hypoxia promoted HCC cell migration and invasion and distant pulmonary metastases, whereas Cav1 silencing abolished these effects. Gene expression profiling revealed that hypoxia-induced Cav1 functioned as a positive regulator of S100P via activation of the NF-κB pathway. S100P elevation under hypoxic conditions was abrogated by silencing of Cav1 or NF-κB function. Conversely, restoring S100P in Cav1-silenced cells rescued the migratory potential of HCC cells along with tumor formation and lung metastasis. In clinical specimens of HCC, we observed S100P overexpression to correlate with venous invasion, microsatellites, direct liver invasion, and absence of tumor encapsulation. Collectively, our findings demonstrated how hypoxia-induced expression of Cav1 in HCC cells enhances their invasive and metastatic potential.
Persistent Identifierhttp://hdl.handle.net/10722/237050
ISSN
2023 Impact Factor: 12.5
2023 SCImago Journal Rankings: 3.468
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMao, X-
dc.contributor.authorWong, SY-
dc.contributor.authorTse, EY-
dc.contributor.authorKo, FCF-
dc.contributor.authorTey, SK-
dc.contributor.authorYeung, YS-
dc.contributor.authorMan, K-
dc.contributor.authorLo, CLR-
dc.contributor.authorNg, IOL-
dc.contributor.authorYam, JWP-
dc.date.accessioned2016-12-20T06:15:32Z-
dc.date.available2016-12-20T06:15:32Z-
dc.date.issued2016-
dc.identifier.citationCancer Research, 2016, v. 76 n. 24, p. 7242-7253-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/237050-
dc.description.abstractIn solid tumors, hypoxia triggers an aberrant vasculogenesis, enhances malignant character, and elevates metastatic risk. The plasma membrane organizing protein caveolin-1 (Cav1) is increased in a variety of cancers, including hepatocellular carcinoma (HCC), where it contributes to metastatic capability. However, the reason for elevation of Cav1 in tumor cells and the mechanistic basis for its contributions to metastatic risk are not fully understood. Here, we show that in HCC cells, hypoxia elevates expression of Cav1, which then acts through the calcium-binding protein S100P to promote metastasis. Hypoxic regions of HCC xenografts displayed elevated expression of Cav1. Hypoxia promoted HCC cell migration and invasion and distant pulmonary metastases, whereas Cav1 silencing abolished these effects. Gene expression profiling revealed that hypoxia-induced Cav1 functioned as a positive regulator of S100P via activation of the NF-κB pathway. S100P elevation under hypoxic conditions was abrogated by silencing of Cav1 or NF-κB function. Conversely, restoring S100P in Cav1-silenced cells rescued the migratory potential of HCC cells along with tumor formation and lung metastasis. In clinical specimens of HCC, we observed S100P overexpression to correlate with venous invasion, microsatellites, direct liver invasion, and absence of tumor encapsulation. Collectively, our findings demonstrated how hypoxia-induced expression of Cav1 in HCC cells enhances their invasive and metastatic potential.-
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.titleMechanisms through which hypoxia-induced caveolin-1 drives tumorigenesis and metastasis in hepatocellular carcinoma-
dc.typeArticle-
dc.identifier.emailMao, X: susanmao@hku.hk-
dc.identifier.emailKo, FCF: bokcf@hku.hk-
dc.identifier.emailTey, SK: szekeong@hku.hk-
dc.identifier.emailYeung, YS: yeungys@hku.hk-
dc.identifier.emailMan, K: kwanman@hku.hk-
dc.identifier.emailLo, CLR: loregina@hku.hk-
dc.identifier.emailNg, IOL: iolng@hku.hk-
dc.identifier.emailYam, JWP: judyyam@pathology.hku.hk-
dc.identifier.authorityMan, K=rp00417-
dc.identifier.authorityLo, CLR=rp01359-
dc.identifier.authorityNg, IOL=rp00335-
dc.identifier.authorityYam, JWP=rp00468-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/0008-5472.CAN-16-1031-
dc.identifier.pmid27784747-
dc.identifier.scopuseid_2-s2.0-85006958084-
dc.identifier.hkuros270736-
dc.identifier.volume76-
dc.identifier.issue24-
dc.identifier.spage7242-
dc.identifier.epage7253-
dc.identifier.isiWOS:000391470600017-
dc.publisher.placeUnited States-
dc.identifier.issnl0008-5472-

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