PIM1 kinase promotes gallbladder cancer cell proliferation via inhibition of proline-rich Akt substrate of 40kDa (PRAS40)

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dc.contributor.authorSubbannayya, Tejaswini
dc.contributor.authorLeal-Rojas, Pamela
dc.contributor.authorZhavoronkov, Alex
dc.contributor.authorOzerov, Ivan, V
dc.contributor.authorKorzinkin, Mikhail
dc.contributor.authorBabu, Niraj
dc.contributor.authorRadhakrishnan, Aneesha
dc.contributor.authorChavan, Sandip
dc.contributor.authorRaja, Remya
dc.contributor.authorPinto, Sneha M.
dc.contributor.authorPatil, Arun H.
dc.contributor.authorBarbhuiya, Mustafa A.
dc.contributor.authorKumar, Prashant
dc.contributor.authorGuerrero-Preston, Rafael
dc.contributor.authorNavani, Sanjay
dc.contributor.authorTiwari, Pramod K.
dc.contributor.authorKumar, Rekha Vijay
dc.contributor.authorPrasad, T. S. Keshava
dc.contributor.authorRoa, Juan Carlos
dc.contributor.authorPandey, Akhilesh
dc.contributor.authorSidransky, David
dc.contributor.authorGowda, Harsha
dc.contributor.authorIzumchenko, Evgeny
dc.contributor.authorChatterjee, Aditi
dc.date.accessioned2025-01-23T21:15:28Z
dc.date.available2025-01-23T21:15:28Z
dc.date.issued2019
dc.description.abstractGallbladder cancer (GBC) is a rare malignancy, associated with poor disease prognosis with a 5-year survival of only 20%. This has been attributed to late presentation of the disease, lack of early diagnostic markers and limited efficacy of therapeutic interventions. Elucidation of molecular events in GBC can contribute to better management of the disease by aiding in the identification of therapeutic targets. To identify aberrantly activated signaling events in GBC, tandem mass tag-based quantitative phosphoproteomic analysis of five GBC cell lines was carried out. Proline-rich Akt substrate 40kDa (PRAS40) was one of the proteins found to be hyperphosphorylated in all the invasive GBC cell lines. Tissue microarray-based immunohistochemical labeling of phospho-PRAS40 (T246) revealed moderate to strong staining in 77% of the primary gallbladder adenocarcinoma cases. Regulation of PRAS40 activity by inhibiting its upstream kinase PIM1 resulted in a significant decrease in cell proliferation, colony forming and invasive ability of GBC cells. Our results support the role of PRAS40 phosphorylation in GBC cell survival and aggressiveness. This study also elucidates phospho-PRAS40 as a clinical marker in GBC and the role of PIM1 as a therapeutic target in GBC.
dc.fuente.origenWOS
dc.identifier.doi10.1007/s12079-018-00503-5
dc.identifier.eissn1873-961X
dc.identifier.issn1873-9601
dc.identifier.urihttps://doi.org/10.1007/s12079-018-00503-5
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/101089
dc.identifier.wosidWOS:000466892100003
dc.issue.numero2
dc.language.isoen
dc.pagina.final177
dc.pagina.inicio163
dc.revistaJournal of cell communication and signaling
dc.rightsacceso restringido
dc.subjectCell survival
dc.subjectGastrointestinal cancer
dc.subjectmTOR signaling
dc.subjectPhosphoproteomics
dc.subjectSGI-1776
dc.subjectTargeted therapy
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePIM1 kinase promotes gallbladder cancer cell proliferation via inhibition of proline-rich Akt substrate of 40kDa (PRAS40)
dc.typeartículo
dc.volumen13
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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