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

Show full item record



Permalink

http://hdl.handle.net/10138/329187

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

Title: ANO1 Expression Orchestrates p27Kip1/MCL1-Mediated Signaling in Head and Neck Squamous Cell Carcinoma
Author: Filippou, Artemis; Pehkonen, Henna; Karhemo, Piia-Riitta; Väänänen, Juho; Nieminen, Anni I.; Klefström, Juha; Grenman, Reidar; Mäkitie, Antti; Joensuu, Heikki; Monni, Outi
Other contributor: University of Helsinki, ATG - Applied Tumor Genomics
University of Helsinki, Research Programs Unit
University of Helsinki, Outi Monni / Principal Investigator
University of Helsinki, Research Programs Unit
University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, HUS Head and Neck Center
University of Helsinki, Heikki Joensuu / Principal Investigator
University of Helsinki, Department of Oncology












Date: 2021-03-09
Language: eng
Number of pages: 21
Belongs to series: Cancers
ISSN: 2072-6694
DOI: https://doi.org/10.3390/cancers13051170
URI: http://hdl.handle.net/10138/329187
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.
Subject: 3122 Cancers
ANO1
head and neck cancer
p27(Kip1)
MCL1
intrinsic apoptosis
cell cycle
targeted therapy
Ani9-5f
AZD-5991
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
cancers_13_01170_v2.pdf 2.354Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record