File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: p85β regulates autophagic degradation of AXL to activate oncogenic signaling

Titlep85β regulates autophagic degradation of AXL to activate oncogenic signaling
Authors
Keywords3d spheroid based drug sensitivity assay
animal cell
autophagy (cellular)
bioassay
carcinogenesis
Issue Date2020
PublisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html
Citation
Nature Communications, 2020, v. 11, p. article no. 2291 How to Cite?
AbstractPIK3R2 encodes the p85β regulatory subunit of phosphatidylinositol 3-kinase and is frequently amplified in cancers. The signaling mechanism and therapeutic implication of p85β are poorly understood. Here we report that p85β upregulates the protein level of the receptor tyrosine kinase AXL to induce oncogenic signaling in ovarian cancer. p85β activates p110 activity and AKT-independent PDK1/SGK3 signaling to promote tumorigenic phenotypes, which are all abolished upon inhibition of AXL. At the molecular level, p85β alters the phosphorylation of TRIM2 (an E3 ligase) and optineurin (an autophagy receptor), which mediate the selective regulation of AXL by p85β, thereby disrupting the autophagic degradation of the AXL protein. Therapeutically, p85β expression renders ovarian cancer cells vulnerable to inhibitors of AXL, p110, or PDK1. Conversely, p85β-depleted cells are less sensitive to these inhibitors. Together, our findings provide a rationale for pharmacological blockade of the AXL signaling axis in PIK3R2-amplified ovarian cancer.
Persistent Identifierhttp://hdl.handle.net/10722/283699
ISSN
2023 Impact Factor: 14.7
2023 SCImago Journal Rankings: 4.887
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorRAO, L-
dc.contributor.authorMak, VCY-
dc.contributor.authorZhou, Y-
dc.contributor.authorZhang, D-
dc.contributor.authorLI, X-
dc.contributor.authorFung, CCY-
dc.contributor.authorSharma, R-
dc.contributor.authorGu, C-
dc.contributor.authorLu, Y-
dc.contributor.authorTipoe, GL-
dc.contributor.authorCheung, ANY-
dc.contributor.authorMills, GB-
dc.contributor.authorCheung, LWT-
dc.date.accessioned2020-07-03T08:22:51Z-
dc.date.available2020-07-03T08:22:51Z-
dc.date.issued2020-
dc.identifier.citationNature Communications, 2020, v. 11, p. article no. 2291-
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10722/283699-
dc.description.abstractPIK3R2 encodes the p85β regulatory subunit of phosphatidylinositol 3-kinase and is frequently amplified in cancers. The signaling mechanism and therapeutic implication of p85β are poorly understood. Here we report that p85β upregulates the protein level of the receptor tyrosine kinase AXL to induce oncogenic signaling in ovarian cancer. p85β activates p110 activity and AKT-independent PDK1/SGK3 signaling to promote tumorigenic phenotypes, which are all abolished upon inhibition of AXL. At the molecular level, p85β alters the phosphorylation of TRIM2 (an E3 ligase) and optineurin (an autophagy receptor), which mediate the selective regulation of AXL by p85β, thereby disrupting the autophagic degradation of the AXL protein. Therapeutically, p85β expression renders ovarian cancer cells vulnerable to inhibitors of AXL, p110, or PDK1. Conversely, p85β-depleted cells are less sensitive to these inhibitors. Together, our findings provide a rationale for pharmacological blockade of the AXL signaling axis in PIK3R2-amplified ovarian cancer.-
dc.languageeng-
dc.publisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html-
dc.relation.ispartofNature Communications-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subject3d spheroid based drug sensitivity assay-
dc.subjectanimal cell-
dc.subjectautophagy (cellular)-
dc.subjectbioassay-
dc.subjectcarcinogenesis-
dc.titlep85β regulates autophagic degradation of AXL to activate oncogenic signaling-
dc.typeArticle-
dc.identifier.emailMak, VCY: vicmak8@hku.hk-
dc.identifier.emailZhou, Y: yzhou@hku.hk-
dc.identifier.emailSharma, R: rasharma@hku.hk-
dc.identifier.emailTipoe, GL: tgeorge@hku.hk-
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hk-
dc.identifier.emailCheung, LWT: lydiacwt@hku.hk-
dc.identifier.authorityTipoe, GL=rp00371-
dc.identifier.authorityCheung, ANY=rp00542-
dc.identifier.authorityCheung, LWT=rp02137-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41467-020-16061-7-
dc.identifier.pmid32385243-
dc.identifier.pmcidPMC7210311-
dc.identifier.scopuseid_2-s2.0-85084721513-
dc.identifier.hkuros310720-
dc.identifier.hkuros319158-
dc.identifier.volume11-
dc.identifier.spagearticle no. 2291-
dc.identifier.epagearticle no. 2291-
dc.identifier.isiWOS:000533936800015-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl2041-1723-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats