Liprin-α1 modulates cancer cell signaling by transmembrane protein CD82 in adhesive membrane domains linked to cytoskeleton

Autor: Pernilla von Nandelstadh, Artemis Filippou, Outi Monni, Mira Lento, Henna Pehkonen, Kaisa Lehti, Reidar Grénman
Přispěvatelé: Genome-Scale Biology (GSB) Research Program, Department of Biochemistry and Developmental Biology, Research Programs Unit, University of Helsinki, Medicum, Kaisa Irene Lehti / Principal Investigator
Rok vydání: 2018
Předmět:
0301 basic medicine
INVASION
lcsh:Medicine
Kangai-1 Protein
Biochemistry
Metastasis
Breast cancer
CD82
Liprin-alpha 1
Neoplasm Metastasis
Head and neck cancer
LIPRIN-ALPHA
Cytoskeleton
Gene knockdown
lcsh:Cytology
Adhesiveness
11Q13 AMPLIFICATION
RNA sequencing
Transmembrane protein
3. Good health
Cell biology
ACTIVE ZONE
Gene Knockdown Techniques
Three-dimensional cell culture
Signal transduction
Liprin-α1
Signal Transduction
PPFIA1
EXPRESSION
CARCINOMA
Breast Neoplasms
Biology
03 medical and health sciences
Membrane Microdomains
POOR-PROGNOSIS
Cell Line
Tumor
EXTRACELLULAR-MATRIX
medicine
Humans
BREAST-CANCER
lcsh:QH573-671
Molecular Biology
Adaptor Proteins
Signal Transducing
Squamous Cell Carcinoma of Head and Neck
Research
lcsh:R
Cancer
Cell Biology
medicine.disease
030104 developmental biology
Cancer cell
ORAL-CANCER
1182 Biochemistry
cell and molecular biology
3111 Biomedicine
Zdroj: Cell Communication and Signaling : CCS
Cell Communication and Signaling, Vol 16, Iss 1, Pp 1-14 (2018)
ISSN: 1478-811X
DOI: 10.1186/s12964-018-0253-y
Popis: Background PPFIA1 is located at the 11q13 region commonly amplified in cancer. The protein liprin-α1 encoded by PPF1A1 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-α1 function in cancer progression has remained elusive. Methods Invasion regulating activity of liprin-α1 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-α1 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-α1 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-α1 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-α1 in biological processes essential in cancer progression. The results reveal liprin-α1 as a novel regulator of CD82, linking liprin-α1 to the cancer cell invasion and metastasis pathways. Electronic supplementary material The online version of this article (10.1186/s12964-018-0253-y) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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