ANO1 Expression Orchestrates p27Kip1/MCL1-Mediated Signaling in Head and Neck Squamous Cell Carcinoma

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dc.contributor.author Filippou, Artemis
dc.contributor.author Pehkonen, Henna
dc.contributor.author Karhemo, Piia-Riitta
dc.contributor.author Väänänen, Juho
dc.contributor.author Nieminen, Anni I.
dc.contributor.author Klefström, Juha
dc.contributor.author Grenman, Reidar
dc.contributor.author Mäkitie, Antti
dc.contributor.author Joensuu, Heikki
dc.contributor.author Monni, Outi
dc.date.accessioned 2021-04-20T09:48:01Z
dc.date.available 2021-04-20T09:48:01Z
dc.date.issued 2021-03-09
dc.identifier.citation Filippou , A , Pehkonen , H , Karhemo , P-R , Väänänen , J , Nieminen , A I , Klefström , J , Grenman , R , Mäkitie , A , Joensuu , H & Monni , O 2021 , ' ANO1 Expression Orchestrates p27Kip1/MCL1-Mediated Signaling in Head and Neck Squamous Cell Carcinoma ' , Cancers , vol. 13 , no. 5 , 1170 . https://doi.org/10.3390/cancers13051170
dc.identifier.other PURE: 162362469
dc.identifier.other PURE UUID: 66b97ffd-44e6-45d5-bde8-e81414e65a2d
dc.identifier.other WOS: 000627933200001
dc.identifier.other Scopus: 85102113843
dc.identifier.other ORCID: /0000-0003-0281-2507/work/92525123
dc.identifier.other ORCID: /0000-0002-4106-1059/work/92527823
dc.identifier.uri http://hdl.handle.net/10138/329187
dc.description.abstract Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors that derive from the mucosal epithelium of the upper aerodigestive tract and present high mortality rate. Lack of efficient targeted-therapies and biomarkers towards patients' stratification are caveats in the disease treatment. Anoctamin 1 (ANO1) gene is amplified in 30% of HNSCC cases. Evidence suggests involvement of ANO1 in proliferation, migration, and evasion of apoptosis; however, the exact mechanisms remain elusive. Aim of this study was to unravel the ANO1-dependent transcriptional programs and expand the existing knowledge of ANO1 contribution to oncogenesis and drug response in HNSCC. We cultured two HNSCC cell lines established from primary tumors harboring amplification and high expression of ANO1 in three-dimensional collagen. Differential expression analysis of ANO1-depleted HNSCC cells demonstrated downregulation of MCL1 and simultaneous upregulation of p27Kip1 expression. Suppressing ANO1 expression led to redistribution of p27Kip1 from the cytoplasm to the nucleus and associated with a cell cycle arrested phenotype. ANO1 silencing or pharmacological inhibition resulted in reduction of cell viability and ANO1 protein levels, as well as suppression of pro-survival BCL2 family proteins. Collectively, these data provide insights of ANO1 involvement in HNSCC carcinogenesis and support the rationale that ANO1 is an actionable drug target. en
dc.format.extent 21
dc.language.iso eng
dc.relation.ispartof Cancers
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject 3122 Cancers
dc.subject ANO1
dc.subject head and neck cancer
dc.subject p27(Kip1)
dc.subject MCL1
dc.subject intrinsic apoptosis
dc.subject cell cycle
dc.subject targeted therapy
dc.subject Ani9-5f
dc.subject AZD-5991
dc.title ANO1 Expression Orchestrates p27Kip1/MCL1-Mediated Signaling in Head and Neck Squamous Cell Carcinoma en
dc.type Article
dc.contributor.organization ATG - Applied Tumor Genomics
dc.contributor.organization Research Programs Unit
dc.contributor.organization Faculty of Medicine
dc.contributor.organization University of Helsinki
dc.contributor.organization Outi Monni / Principal Investigator
dc.contributor.organization CAN-PRO - Translational Cancer Medicine Program
dc.contributor.organization Medicum
dc.contributor.organization HUS Head and Neck Center
dc.contributor.organization Department of Ophthalmology and Otorhinolaryngology
dc.contributor.organization Clinicum
dc.contributor.organization Heikki Joensuu / Principal Investigator
dc.contributor.organization HUS Comprehensive Cancer Center
dc.contributor.organization Department of Oncology
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.3390/cancers13051170
dc.relation.issn 2072-6694
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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