The paxillin-plectin-EPLIN complex promotes apical elimination of RasV12-transformed cells by modulating HDAC6-regulated tubulin acetylation

Nobuhiro Kasai, Ailijiang Kadeer, Mihoko Kajita, Sayaka Saitoh, Susumu Ishikawa, Takeshi Maruyama, Yasuyuki Fujita

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Recent studies have revealed that newly emerging RasV12-transformed cells are often apically extruded from the epithelial layer. During this cancer preventive process, cytoskeletal proteins plectin and Epithelial Protein Lost In Neoplasm (EPLIN) are accumulated in RasV12 cells that are surrounded by normal cells, which positively regulate the apical elimination of transformed cells. However, the downstream regulators of the plectin-EPLIN complex remain to be identified. In this study, we have found that paxillin binds to EPLIN specifically in the mix culture of normal and RasV12-transformed cells. In addition, paxillin is accumulated in RasV12 cells surrounded by normal cells. Paxillin, plectin and EPLIN mutually influence their non-cell-autonomous accumulation, and paxillin plays a crucial role in apical extrusion of RasV12 cells. We also demonstrate that in RasV12 cells surrounded by normal cells, acetylated tubulin is accumulated. Furthermore, acetylation of tubulin is promoted by paxillin that suppresses the activity of histone deacetylase (HDAC) 6. Collectively, these results indicate that in concert with plectin and EPLIN, paxillin positively regulates apical extrusion of RasV12-transformed cells by promoting microtubule acetylation. This study shed light on the unexplored events occurring at the initial stage of carcinogenesis and would potentially lead to a novel type of cancer preventive medicine.

Original languageEnglish
Article number2097
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1
Externally publishedYes

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Plectin
Paxillin
Tubulin
Acetylation
Neoplasms
Proteins
Preventive Medicine
Histone Deacetylases
Cytoskeletal Proteins
Microtubules

ASJC Scopus subject areas

  • General

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The paxillin-plectin-EPLIN complex promotes apical elimination of RasV12-transformed cells by modulating HDAC6-regulated tubulin acetylation. / Kasai, Nobuhiro; Kadeer, Ailijiang; Kajita, Mihoko; Saitoh, Sayaka; Ishikawa, Susumu; Maruyama, Takeshi; Fujita, Yasuyuki.

In: Scientific Reports, Vol. 8, No. 1, 2097, 01.12.2018.

Research output: Contribution to journalArticle

Kasai, Nobuhiro ; Kadeer, Ailijiang ; Kajita, Mihoko ; Saitoh, Sayaka ; Ishikawa, Susumu ; Maruyama, Takeshi ; Fujita, Yasuyuki. / The paxillin-plectin-EPLIN complex promotes apical elimination of RasV12-transformed cells by modulating HDAC6-regulated tubulin acetylation. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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