Adhesion molecule periplakin is involved in cellular movement and attachment in pharyngeal squamous cancer cells

Yurie Tonoike,Yukio Nakatani,Fumio Nomura,Takeshi Tomonaga,Kazuyuki Matsushita,Nobuko Tanaka,Hideaki Shimada,Yoshitaka Okamoto,Koji Katada

doi:10.1186/1471-2121-12-41

Abstract

BackgroundWe previously reported that periplakin (PPL) is downregulated in human esophageal cancer tissues compared to the adjacent non-cancer epithelium. Thus PPL could be a useful marker for detection of early esophageal cancer and evaluation of tumor progression, but largely remains unknown in this field. To investigate PPL involvement in carcinogenesis, tumor progression, cellular movement or attachment activity, siRNAs against PPL were transfected into pharyngeal squamous cancer cell lines and their effects on cellular behaviours were examined.ResultsPPL knockdown appeared to decrease tumor cell growth together with G2/M phase accumulation in cells attached to a culture dish. However, the extent of cell growth suppression, evaluated by the number of cells attached to the culture dish, was too distinctive to be explained only by cell cycle delay. Importantly, PPL knockdown suppressed cellular movement and attachment to the culture dish accompanied by decreased pAktSer473 phosphorylation. Additionally, LY294002, a PI3K inhibitor that dephosphorylates pAktSer473, significantly suppressed D562 cell migration. Thus PPL potentially engages in cellular movement al least partly via the PI3K/Akt axis.ConclusionsPPL knockdown is related to reduced cellular movement and attachment activity in association with PI3K/Akt axis suppression, rather than malignant progression in pharyngeal cancer cells.

Highlights

We previously reported that periplakin (PPL) is downregulated in human esophageal cancer tissues compared to the adjacent non-cancer epithelium
We found that PPL knockdown was related to a reduction in cellular movement and attachment activity, and was accompanied by phosphatidylinositol 3’ kinase (PI3K)/ Akt axis suppression in pharyngeal cancer cells; it was potentially related to epithelial-mesenchymal transition (EMT) promotion
Knockdown of PPL expression reduced the number of cells attached to the culture dish Since PPL expression is decreased in esophageal carcinoma tissues [2], we tried to determine the effects of PPL downregulation on cancer cell activities

Summary

Introduction

We previously reported that periplakin (PPL) is downregulated in human esophageal cancer tissues compared to the adjacent non-cancer epithelium. We previously reported that a cell adhesion molecule, periplakin (PPL), is significantly downregulated in human esophageal cancers. PPL expression has been associated with nodal metastasis [3] These findings indicate that PPL plays an important role in the development of esophageal and pharyngeal squamous cell carcinoma; the precise mechanism remains largely unknown. PPL is a member of the plakin family comprising desmoplakin, envoplakin, plectin, and bullous pemphigoid antigen 1, which have various functions in connecting cytoskeleton elements to form intercellular junction complexes [4]. PPL plays a role as a localization signal in oncogenic serine/threonine protein kinase Akt/protein kinase B (PKB)-mediated signaling in human cancer cell lines [7]. Activation of the PI3K/Akt/ PKB pathway is emerging as a central feature of epithelial-mesenchymal transition (EMT), which is believed to be a crucial event in tumor development [8]

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