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- Publisher Website: 10.1038/s41467-019-08574-7
- Scopus: eid_2-s2.0-85061500872
- PMID: 30755611
- WOS: WOS:000458398900010
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Article: Deregulated Gab2 phosphorylation mediates aberrant AKT and STAT3 signaling upon PIK3R1 loss in ovarian cancer
Title | Deregulated Gab2 phosphorylation mediates aberrant AKT and STAT3 signaling upon PIK3R1 loss in ovarian cancer |
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Authors | |
Keywords | Akt signaling animal experiment animal model animal tissue antineoplastic activity |
Issue Date | 2019 |
Publisher | Nature 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, 2019, v. 10, p. article no. 716 How to Cite? |
Abstract | Copy number loss of PIK3R1 (p85α) most commonly occurs in ovarian cancer among all cancer types. Here we report that ovarian cancer cells manifest a spectrum of tumorigenic phenotypes upon knockdown of PIK3R1. PIK3R1 loss activates AKT and p110-independent JAK2/STAT3 signaling through inducing changes in the phosphorylation of the docking protein Gab2, thereby relieving the negative inhibition on AKT and promoting the assembly of JAK2/STAT3 signalosome, respectively. Additional mechanisms leading to AKT activation include enhanced p110α kinase activity and a decrease in PTEN level. PIK3R1 loss renders ovarian cancer cells vulnerable to inhibition of AKT or JAK2/STAT3. The combination of AKT and STAT3 inhibitors significantly increases the anti-tumor effect compared to single-agent treatments. Together, our findings provide a rationale for mechanism-based therapeutic approach that targets tumors with loss of PIK3R1. |
Persistent Identifier | http://hdl.handle.net/10722/271375 |
ISSN | 2023 Impact Factor: 14.7 2023 SCImago Journal Rankings: 4.887 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | LI, X | - |
dc.contributor.author | Mak, VCY | - |
dc.contributor.author | Zhou, Y | - |
dc.contributor.author | Wang, C | - |
dc.contributor.author | Wong, ESY | - |
dc.contributor.author | Sharma, R | - |
dc.contributor.author | Lu, Y | - |
dc.contributor.author | Cheung, ANY | - |
dc.contributor.author | Mills, GB | - |
dc.contributor.author | Cheung, LWT | - |
dc.date.accessioned | 2019-06-24T01:08:39Z | - |
dc.date.available | 2019-06-24T01:08:39Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Nature Communications, 2019, v. 10, p. article no. 716 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | http://hdl.handle.net/10722/271375 | - |
dc.description.abstract | Copy number loss of PIK3R1 (p85α) most commonly occurs in ovarian cancer among all cancer types. Here we report that ovarian cancer cells manifest a spectrum of tumorigenic phenotypes upon knockdown of PIK3R1. PIK3R1 loss activates AKT and p110-independent JAK2/STAT3 signaling through inducing changes in the phosphorylation of the docking protein Gab2, thereby relieving the negative inhibition on AKT and promoting the assembly of JAK2/STAT3 signalosome, respectively. Additional mechanisms leading to AKT activation include enhanced p110α kinase activity and a decrease in PTEN level. PIK3R1 loss renders ovarian cancer cells vulnerable to inhibition of AKT or JAK2/STAT3. The combination of AKT and STAT3 inhibitors significantly increases the anti-tumor effect compared to single-agent treatments. Together, our findings provide a rationale for mechanism-based therapeutic approach that targets tumors with loss of PIK3R1. | - |
dc.language | eng | - |
dc.publisher | Nature 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.ispartof | Nature Communications | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Akt signaling | - |
dc.subject | animal experiment | - |
dc.subject | animal model | - |
dc.subject | animal tissue | - |
dc.subject | antineoplastic activity | - |
dc.title | Deregulated Gab2 phosphorylation mediates aberrant AKT and STAT3 signaling upon PIK3R1 loss in ovarian cancer | - |
dc.type | Article | - |
dc.identifier.email | Mak, VCY: vicmak8@hku.hk | - |
dc.identifier.email | Zhou, Y: yzhou@hku.hk | - |
dc.identifier.email | Wong, ESY: esywong@hkucc.hku.hk | - |
dc.identifier.email | Sharma, R: rasharma@hku.hk | - |
dc.identifier.email | Cheung, ANY: anycheun@hkucc.hku.hk | - |
dc.identifier.email | Cheung, LWT: lydiacwt@hku.hk | - |
dc.identifier.authority | Cheung, ANY=rp00542 | - |
dc.identifier.authority | Cheung, LWT=rp02137 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1038/s41467-019-08574-7 | - |
dc.identifier.pmid | 30755611 | - |
dc.identifier.pmcid | PMC6372715 | - |
dc.identifier.scopus | eid_2-s2.0-85061500872 | - |
dc.identifier.hkuros | 298104 | - |
dc.identifier.volume | 10 | - |
dc.identifier.spage | article no. 716 | - |
dc.identifier.epage | article no. 716 | - |
dc.identifier.isi | WOS:000458398900010 | - |
dc.publisher.place | United Kingdom | - |
dc.identifier.issnl | 2041-1723 | - |