Prognostic and therapeutic value of the Hippo pathway, RABL6A, and p53-MDM2 axes in sarcomas.
RABL6A
TAZ
YAP
p53-MDM2
sarcoma
Journal
Oncotarget
ISSN: 1949-2553
Titre abrégé: Oncotarget
Pays: United States
ID NLM: 101532965
Informations de publication
Date de publication:
13 Apr 2021
13 Apr 2021
Historique:
received:
12
02
2021
accepted:
15
03
2021
entrez:
23
4
2021
pubmed:
24
4
2021
medline:
24
4
2021
Statut:
epublish
Résumé
Additional prognostic and therapeutic biomarkers effective across different histological types of sarcoma are needed. Herein we evaluate expression of TAZ and YAP, the p53-MDM2 axis, and RABL6A, a novel oncoprotein with potential ties to both pathways, in sarcomas of different histological types. Immunohistochemical staining of a tissue microarray including 163 sarcomas and correlation with clinical data showed that elevated YAP and TAZ independently predict worse overall and progression-free survival, respectively. In the absence of p53 expression, combined TAZ and YAP expression adversely affect overall, progression free, and metastasis free survival more than TAZ or YAP activation alone. RABL6A independently predicted shorter time to metastasis and was positively correlated with p53, MDM2 and YAP expression, supporting a possible functional relationship between the biomarkers. Network analysis further showed that TAZ is positively correlated with MDM2 expression. The data implicate all five proteins as clinically relevant downstream players in the Hippo pathway. Finally, a novel inhibitor of MDM2 (MA242), effectively suppressed the survival of sarcoma cell lines from different histological types regardless of p53 status. These findings suggest both independent and cooperative roles for all five biomarkers across different histological types of sarcoma in predicting patient outcomes and potentially guiding future therapeutic approaches.
Identifiants
pubmed: 33889298
doi: 10.18632/oncotarget.27928
pii: 27928
pmc: PMC8057271
doi:
Types de publication
Journal Article
Langues
eng
Pagination
740-755Subventions
Organisme : BLRD VA
ID : I01 BX003644
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA086862
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA237031
Pays : United States
Informations de copyright
Copyright: © 2021 Desai et al.
Déclaration de conflit d'intérêts
CONFLICTS OF INTEREST Authors have no conflicts of interest to declare.
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