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

Henna Pehkonen,Outi Monni,Kaisa Lehti,Kaisa Lehti,Kaisa Lehti,Pernilla Von Nandelstadh,Piia-Riitta Karhemo,Tatiana Lepikhova,Reidar Grenman

doi:10.1038/srep24486

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-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 filament network, thereby altering the invasion and growth properties of the cancer cells. In non-invasive cells liprin-α1 promotes expansive growth behavior with limited invasive capacity, whereas in invasive cells liprin-α1 has significant impact on mesenchymal cancer cell invasion in three-dimensional collagen. Current results identify liprin-α1 as a novel regulator of the tumor cell intermediate filaments with differential oncogenic properties in actively proliferating or motile cells.

Highlights

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
Liprin-α 1 is encoded by PPFIA1 located at the 11q13 locus, which is one of the most commonly amplified region in several epithelial cancers such as those arising in head and neck[1,2], breast[3,4], and ovarian cancer[5,6]
Contradictory results have been reported regarding the effects of liprin-α 1 on the motility of head and neck squamous cell carcinoma (HNSCC) and breast cancer cell lines (Table 1)[10,11], both these cell types display frequent 11q13 amplification

Summary

Introduction

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. Our results indicate that liprin-α1 localizes to different adhesion and cytoskeletal structures to regulate vimentin intermediate filament network, thereby altering the invasion and growth properties of the cancer cells. Liprin-α 1 is encoded by PPFIA1 located at the 11q13 locus, which is one of the most commonly amplified region in several epithelial cancers such as those arising in head and neck[1,2], breast[3,4], and ovarian cancer[5,6]. Regulation of focal adhesion dynamics is a complex process that involves interplay of various proteins, including those at the actin cytoskeleton and vimentin intermediate filament networks, which are interlinked in an adhesion dependent manner[21]. Description of the cell line breast adenocarcinoma breast carcinoma head and neck squamous cell carcinoma head and neck squamous cell carcinoma head and neck squamous cell carcinoma head and neck squamous cell carcinoma head and neck squamous cell carcinoma head and neck squamous cell carcinoma head and neck squamous cell carcinoma head and neck squamous cell carcinoma

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