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

PPL 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.PPL 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.Pharyngeal and esophageal cancers are some of the most malignant gastrointestinal tumors [1]. We previously reported that a cell adhesion molecule, periplakin (PPL), is significantly downregulated in human esophageal cancers. Immunohistochemical staining has also revealed that PPL changes its cellular localization as well as its expression levels with cancer progression [2]. In addition, 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; however, 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]. Plakin families also function as "molecular bridges" of cells that link the intracellular cytoskeleton and cell-cell junctions. For example, plectin, one of the most well-studied plakins, directly interacts with signal transductions [5,6]. PPL also plays a role as a localization signal in oncog