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Liprin-?1 is a regulator of vimentin intermediate filament network in the cancer cell adhesion machinery.

ABSTRACT: PPFIA1 is located at the 11q13 region, which is one of the most commonly amplified regions in several epithelial cancers including head and neck squamous cell carcinoma and breast carcinoma. Considering the location of PPFIA1 in this amplicon, we examined whether protein encoded by PPFIA1, liprin-?1, possesses oncogenic properties in relevant carcinoma cell lines. Our results indicate that liprin-?1 localizes to different adhesion and cytoskeletal structures to regulate vimentin intermediate filament network, thereby altering the invasion and growth properties of the cancer cells. In non-invasive cells liprin-?1 promotes expansive growth behavior with limited invasive capacity, whereas in invasive cells liprin-?1 has significant impact on mesenchymal cancer cell invasion in three-dimensional collagen. Current results identify liprin-?1 as a novel regulator of the tumor cell intermediate filaments with differential oncogenic properties in actively proliferating or motile cells.

SUBMITTER: Pehkonen H

PROVIDER: S-EPMC4830931 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Liprin-α1 is a regulator of vimentin intermediate filament network in the cancer cell adhesion machinery.

Pehkonen Henna H von Nandelstadh Pernilla P Karhemo Piia-Riitta PR Lepikhova Tatiana T Grenman Reidar R Lehti Kaisa K Monni Outi O

Scientific reports 20160414

PPFIA1 is located at the 11q13 region, which is one of the most commonly amplified regions in several epithelial cancers including head and neck squamous cell carcinoma and breast carcinoma. Considering the location of PPFIA1 in this amplicon, we examined whether protein encoded by PPFIA1, liprin-α1, possesses oncogenic properties in relevant carcinoma cell lines. Our results indicate that liprin-α1 localizes to different adhesion and cytoskeletal structures to regulate vimentin intermediate fil ...[more]

PMID: 27075696

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Project description:BACKGROUND: Human neuroblastoma (NB) cell lines may present with either one of the so-called S-and N-subtypes. We have previously reported a strong correlation between protein expression levels of vimentin, an S-subtype marker, and the p21Waf1 cyclin-dependent kinase inhibitor. We here investigated whether this correlation extend to the mRNA level in NB cell lines as well as in patients' tumors. We also further explored the relationship between expression of vimentin and p21, by asking whether vimentin could regulate p21 expression. METHODS: Vimentin and p21 mRNA levels in NB cell lines as well as in patients' tumors (n = 77) were quantified using Q-PCR. Q-PCR data obtained from tumors of high risk NB patients (n = 40) were analyzed in relation with the overall survival using the Log-rank Kaplan-Meier estimation. siRNA-mediated depletion or overexpression of vimentin in highly or low expressing vimentin cell lines, respectively, followed by protein expression and promoter activation assays were used to assess the role of vimentin in modulating p21 expression. RESULTS: We extend the significant correlation between vimentin and p21 expression to the mRNA level in NB cell lines as well as in patients' tumors. Overall survival analysis from Q-PCR data obtained from tumors of high risk patients suggests that lower levels of p21 expression could be associated with a poorer outcome. Our data additionally indicate that the correlation observed between p21 and vimentin expression levels results from p21 transcriptional activity being regulated by vimentin. Indeed, downregulating vimentin resulted in a significant decrease in p21 mRNA and protein expression as well as in p21 promoter activity. Conversely, overexpressing vimentin triggered an increase in p21 promoter activity in cells with a nuclear expression of vimentin. CONCLUSION: Our results suggest that p21 mRNA tumor expression level could represent a refined prognostic factor for high risk NB patients. Our data also show that vimentin regulates p21 transcription; this is the first demonstration of a gene regulating function for this type III-intermediate filament.

Dataset Information

Liprin-?1 is a regulator of vimentin intermediate filament network in the cancer cell adhesion machinery.

Publications

Liprin-α1 is a regulator of vimentin intermediate filament network in the cancer cell adhesion machinery.

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