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Conference Paper: p70 S6 kinase signals tristetraprolin/Dicer-mediated maturation of microRNA-145 to regulate tumor metastasis

Titlep70 S6 kinase signals tristetraprolin/Dicer-mediated maturation of microRNA-145 to regulate tumor metastasis
Authors
KeywordsMedical sciences
Oncology
Issue Date2014
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
The 2014 Annual Meeting of the American Association for Cancer research (AACR 2014), San Diego, CA., 5-9 April 2014. In Cancer Research, 2014, v. 74 n. 19 suppl., abstract no. 1449 How to Cite?
AbstractOvarian cancer is a highly metastatic tumor characterized by malignant ascites spheroids, which represent one of the most important prognostic factors of poor clinical outcome. Multicellular aggregates known as spheroids (MCS) are important for anchorage-independent growth and metastasis. MCS are also an important phenomenon of cancer stem cells. However, the factors that regulate MCS formation are largely unknown. MicroRNAs (miRNA) are short non-coding RNAs that are critically involved in different oncogenic events by actively modulating mRNA and protein synthesis. Despite their clinical significance, processes regulating miRNA biogenesis remain obscure. Here, we identify N-cadherin as a key regulator of MCS formation activated in response to p70 S6 kinase (p70S6K) signaling, a downstream effector of phosphatidylinositol 3-kinase/Akt which is hyperactive in human ovarian cancer. The results also identify a new mechanism of p70S6K function that mediates microRNA (miR)-145 coregulation of key transcription factors Twist and Sox-9, thereby enhancing N-cadherin and MCS formation. p70S6K regulates miR-145 by deactivating a distinct tristetraprolin (TPP)/Dicer program. The p70S6K phosphorylates TTP, leading to inhibition of interaction between TTP and Dicer and decreased TTP activity in miR-145 processing. Silencing of p70S6K enhances the TTP/Dicer interaction and its activating in regulating miR-145. These results providea novel regulatory mechanism of p70S6K involved in the formation and spread of MCS and insights on the development of new therapeutic targets. (This work was supported by RGC grant HKU782111 and CUHK8/CRF/11R). ©2014 American Association for Cancer Research.
DescriptionMeeting Theme: Harnessing Breakthroughs - Targeting Cures
Session - Molecular and Cellular Biology: Poster Presentations - MicroRNAs and Metastasis: abstract no. 1449
This journal suppl. entitled: Proceedings: AACR Annual Meeting 2014
Persistent Identifierhttp://hdl.handle.net/10722/213532
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorLam, SSN-
dc.contributor.authorIp, CKM-
dc.contributor.authorWong, AST-
dc.date.accessioned2015-08-05T02:18:58Z-
dc.date.available2015-08-05T02:18:58Z-
dc.date.issued2014-
dc.identifier.citationThe 2014 Annual Meeting of the American Association for Cancer research (AACR 2014), San Diego, CA., 5-9 April 2014. In Cancer Research, 2014, v. 74 n. 19 suppl., abstract no. 1449-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/213532-
dc.descriptionMeeting Theme: Harnessing Breakthroughs - Targeting Cures-
dc.descriptionSession - Molecular and Cellular Biology: Poster Presentations - MicroRNAs and Metastasis: abstract no. 1449-
dc.descriptionThis journal suppl. entitled: Proceedings: AACR Annual Meeting 2014-
dc.description.abstractOvarian cancer is a highly metastatic tumor characterized by malignant ascites spheroids, which represent one of the most important prognostic factors of poor clinical outcome. Multicellular aggregates known as spheroids (MCS) are important for anchorage-independent growth and metastasis. MCS are also an important phenomenon of cancer stem cells. However, the factors that regulate MCS formation are largely unknown. MicroRNAs (miRNA) are short non-coding RNAs that are critically involved in different oncogenic events by actively modulating mRNA and protein synthesis. Despite their clinical significance, processes regulating miRNA biogenesis remain obscure. Here, we identify N-cadherin as a key regulator of MCS formation activated in response to p70 S6 kinase (p70S6K) signaling, a downstream effector of phosphatidylinositol 3-kinase/Akt which is hyperactive in human ovarian cancer. The results also identify a new mechanism of p70S6K function that mediates microRNA (miR)-145 coregulation of key transcription factors Twist and Sox-9, thereby enhancing N-cadherin and MCS formation. p70S6K regulates miR-145 by deactivating a distinct tristetraprolin (TPP)/Dicer program. The p70S6K phosphorylates TTP, leading to inhibition of interaction between TTP and Dicer and decreased TTP activity in miR-145 processing. Silencing of p70S6K enhances the TTP/Dicer interaction and its activating in regulating miR-145. These results providea novel regulatory mechanism of p70S6K involved in the formation and spread of MCS and insights on the development of new therapeutic targets. (This work was supported by RGC grant HKU782111 and CUHK8/CRF/11R). ©2014 American Association for Cancer Research.-
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.subjectMedical sciences-
dc.subjectOncology-
dc.titlep70 S6 kinase signals tristetraprolin/Dicer-mediated maturation of microRNA-145 to regulate tumor metastasis-
dc.typeConference_Paper-
dc.identifier.emailIp, CKM: carmanip@hku.hk-
dc.identifier.emailWong, AST: awong1@hku.hk-
dc.identifier.authorityWong, AST=rp00805-
dc.identifier.doi10.1158/1538-7445.AM2014-1449-
dc.identifier.hkuros247713-
dc.identifier.volume74-
dc.identifier.issue19 suppl.-
dc.publisher.placeUnited States-

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