Liprin-alpha 1 modulates cancer cell signaling by transmembrane protein CD82 in adhesive membrane domains linked to cytoskeleton

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http://hdl.handle.net/10138/298866

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Pehkonen , H , Lento , M , von Nandelstadh , P , Filippou , A , Grenman , R , Lehti , K & Monni , O 2018 , ' Liprin-alpha 1 modulates cancer cell signaling by transmembrane protein CD82 in adhesive membrane domains linked to cytoskeleton ' , Cell Communication and Signaling , vol. 16 , no. 1 , 41 . https://doi.org/10.1186/s12964-018-0253-y

Title: Liprin-alpha 1 modulates cancer cell signaling by transmembrane protein CD82 in adhesive membrane domains linked to cytoskeleton
Author: Pehkonen, Henna; Lento, Mira; von Nandelstadh, Pernilla; Filippou, Artemis; Grenman, Reidar; Lehti, Kaisa; Monni, Outi
Contributor: University of Helsinki, Genome-Scale Biology (GSB) Research Program
University of Helsinki, Genome-Scale Biology (GSB) Research Program
University of Helsinki, Genome-Scale Biology (GSB) Research Program
University of Helsinki, Kaisa Irene Lehti / Principal Investigator
University of Helsinki, Genome-Scale Biology (GSB) Research Program
Date: 2018-07-13
Language: eng
Number of pages: 14
Belongs to series: Cell Communication and Signaling
ISSN: 1478-811X
URI: http://hdl.handle.net/10138/298866
Abstract: Background: PPFIA1 is located at the 11q13 region commonly amplified in cancer. The protein liprin-alpha 1 encoded by PPFIA1 contributes to the adhesive and invasive structures of cytoskeletal elements and is located at the invadosomes in cancer cells. However, the precise mechanism of liprin-alpha 1 function in cancer progression has remained elusive. Methods: Invasion regulating activity of liprin-alpha 1 was examined by analyzing the functions of squamous cell carcinoma of head and neck (HNSCC) cell lines in three-dimensional collagen I after RNAi mediated gene knockdown. Transcriptome profiling and Gene Set Enrichment Analysis from HNSCC and breast cancer cells were used to identify expression changes relevant to specific cellular localizations, biological processes and signaling pathways after PPFIA1 knockdown. The significance of the results was assessed by relevant statistical methods (Wald and Benjamini-Hochberg). Localization of proteins associated to liprin-alpha 1 was studied by immunofluorescence in 2D and 3D conditions. The association of PPFIA1 amplification to HNSCC patient survival was explored using The Cancer Genome Atlas data. Results: In this study, we show that liprin-alpha 1 regulates biological processes related to membrane microdomains in breast carcinoma, as well as protein trafficking, cell-cell and cell-substrate contacts in HNSCC cell lines cultured in three-dimensional matrix. Importantly, we show that in all these cancer cells liprin-alpha 1 knockdown leads to the upregulation of transmembrane protein CD82, which is a suppressor of metastasis in several solid tumors. Conclusions: Our results provide novel information regarding the function of liprin-alpha 1 in biological processes essential in cancer progression. The results reveal liprin-alpha 1 as a novel regulator of CD82, linking liprin-alpha 1 to the cancer cell invasion and metastasis pathways.
Subject: Liprin-alpha 1
PPFIA1
CD82
Head and neck cancer
Breast cancer
Invasion
RNA sequencing
Three-dimensional cell culture
BREAST-CANCER
EXTRACELLULAR-MATRIX
POOR-PROGNOSIS
11Q13 AMPLIFICATION
LIPRIN-ALPHA
ORAL-CANCER
ACTIVE ZONE
INVASION
EXPRESSION
CARCINOMA
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
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