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1. Calcium sparks enhance the tissue fluidity within epithelial layers and promote apical extrusion of transformed cells

Author

Kuromiya, Keisuke, Aoki, Kana, Ishibashi, Kojiro, Yotabun, Moe, Sekai, Miho, Tanimura, Nobuyuki, Iijima, Sayuri, Ishikawa, Susumu, Kamasaki, Tomoko, Akieda, Yuki, Ishitani, Tohru, Hayashi, Takashi, Toda, Satoshi, Yokoyama, Koji, Lee, Chol Gyu, Usami, Ippei, Inoue, Haruki, Takigawa, Ichigaku, Gauquelin, Estelle, Sugimura, Kaoru, Hino, Naoya, and Fujita, Yasuyuki

Published
2022
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5. The CD44/COL17A1 pathway promotes the formation of multilayered, transformed epithelia

Author

Kozawa, Kei, Sekai, Miho, Ohba, Kenji, Ito, Shoko, Sako, Hiroaki, Maruyama, Takeshi, Kakeno, Mai, Shirai, Takanobu, Kuromiya, Keisuke, Kamasaki, Tomoko, Kohashi, Koki, Tanaka, Shinya, Ishikawa, Susumu, Sato, Nanami, Asano, Shota, Suzuki, Hironori, Tanimura, Nobuyuki, Mukai, Yohei, Gotoh, Noriko, Tanino, Mishie, Natsuga, Ken, Soga, Tomoyoshi, Nakamura, Tomonori, Yabuta, Yukihiro, Saitou, Mitinori, Ito, Takahiro, Matsuura, Kenkyo, Tsunoda, Makoto, Kikumori, Toyone, Iida, Tadashi, Mizutani, Yasuyuki, Miyai, Yuki, Kaibuchi, Kozo, Enomoto, Atsushi, and Fujita, Yasuyuki

Published
2021
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7. Calcium Wave Promotes Cell Extrusion

Author

Takeuchi, Yasuto, Narumi, Rika, Akiyama, Ryutaro, Vitiello, Elisa, Shirai, Takanobu, Tanimura, Nobuyuki, Kuromiya, Keisuke, Ishikawa, Susumu, Kajita, Mihoko, Tada, Masazumi, Haraoka, Yukinari, Akieda, Yuki, Ishitani, Tohru, Fujioka, Yoichiro, Ohba, Yusuke, Yamada, Sohei, Hosokawa, Yoichiroh, Toyama, Yusuke, Matsui, Takaaki, and Fujita, Yasuyuki

Published
2020
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9. Accumulation of annexin A2 and S100A10 prevents apoptosis of apically delaminated, transformed epithelial cells

Author

Ito, Shoko, primary, Kuromiya, Keisuke, additional, Sekai, Miho, additional, Sako, Hiroaki, additional, Sai, Kazuhito, additional, Morikawa, Riho, additional, Mukai, Yohei, additional, Ida, Yoko, additional, Anzai, Moe, additional, Ishikawa, Susumu, additional, Kozawa, Kei, additional, Shirai, Takanobu, additional, Tanimura, Nobuyuki, additional, Sugie, Kenta, additional, Ikenouchi, Junichi, additional, Ogawa, Motoyuki, additional, Naguro, Isao, additional, Ichijo, Hidenori, additional, and Fujita, Yasuyuki, additional

Published
2023
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13. Bacterial endocarditis caused by contact lens usage.

Author

Ishikawa, Susumu, Matsunaga, Hiroki, Mishima, Hideki, Katayama, Yasushi, Yuri, Koichi, Ohashi, Koichi, and Abe, Daisuke

Subjects
*INFECTIVE endocarditis, *CONTACT lenses, *MITRAL valve surgery, *ECHOCARDIOGRAPHY, *HOSPITAL care
Abstract

A 17-year-old female was transferred to our hospital due to high fever, general fatigue, and dim eyesight. Three weeks before, she had used cosmetic colored contact lenses and then suffered from bloodshot eyes associated with dim eyesight. Intermittent fever and general fatigue were followed by eye symptoms. Echocardiography revealed moving vegetation on the posterior leaflet of the mitral valve associated with mild mitral valve regurgitation. There were no infectious sites in systemic examinations; thus, the cause of infective endocarditis was considered the infection due to contact lens usage. The patient initially received mitral valve plasty associated with the removal of infective sites. However, redo surgery was necessary 19 days later due to the relapse of infection, and the mitral valve was replaced by bioprosthesis. Traumatic injury of vessels due to inappropriate contact lens usage seemed to lead to systemic hematogenous infection and subsequent endocarditis. We report a rare case of infective endocarditis which was caused by contact lens usage. [ABSTRACT FROM AUTHOR]

Published
2024
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15. FBP17-mediated finger-like membrane protrusions in cell competition between normal and RasV12-transformed cells

Author

Kamasaki, Tomoko, Miyazaki, Yumi, Ishikawa, Susumu, Hoshiba, Kazuya, Kuromiya, Keisuke, Tanimura, Nobuyuki, Mori, Yusuke, Tsutsumi, Motosuke, Nemoto, Tomomi, Uehara, Ryota, Suetsugu, Shiro, Itoh, Toshiki, Fujita, Yasuyuki, Kamasaki, Tomoko, Miyazaki, Yumi, Ishikawa, Susumu, Hoshiba, Kazuya, Kuromiya, Keisuke, Tanimura, Nobuyuki, Mori, Yusuke, Tsutsumi, Motosuke, Nemoto, Tomomi, Uehara, Ryota, Suetsugu, Shiro, Itoh, Toshiki, and Fujita, Yasuyuki

Abstract

At the initial stage of carcinogenesis, cell competition often occurs between newly emerging transformed cells and the neighboring normal cells, leading to the elimination of transformed cells from the epithelial layer. For instance, when RasV12-transformed cells are surrounded by normal cells, RasV12 cells are apically extruded from the epithelium. However, the underlying mechanisms of this tumor-suppressive process still remain enigmatic. We first show by electron microscopic analysis that characteristic finger-like membrane protrusions are projected from both normal and RasV12 cells at their interface. In addition, FBP17, a member of the F-BAR proteins, accumulates in RasV12 cells, as well as surrounding normal cells, which plays a positive role in the formation of finger-like protrusions and apical elimination of RasV12 cells. Furthermore, cdc42 acts upstream of these processes. These results suggest that the cdc42/FBP17 pathway is a crucial trigger of cell competition, inducing “protrusion to protrusion response” between normal and RasV12-transformed cells.

Published
2023

19. Calcium sparks enhance the tissue fluidity within epithelial layers and promote apical extrusion of transformed cells

Author

50737533, 00844557, 10374597, 50580974, Kuromiya, Keisuke, Aoki, Kana, Ishibashi, Kojiro, Yotabun, Moe, Sekai, Miho, Tanimura, Nobuyuki, Iijima, Sayuri, Ishikawa, Susumu, Kamasaki, Tomoko, Akieda, Yuki, Ishitani, Tohru, Hayashi, Takashi, Toda, Satoshi, Yokoyama, Koji, Lee, Gyu, Chol, Usami, Ippei, Inoue, Haruki, Takigawa, Ichigaku, Gauquelin, Estelle, Sugimura, Kaoru, Hino, Naoya, Fujita, Yasuyuki, 50737533, 00844557, 10374597, 50580974, Kuromiya, Keisuke, Aoki, Kana, Ishibashi, Kojiro, Yotabun, Moe, Sekai, Miho, Tanimura, Nobuyuki, Iijima, Sayuri, Ishikawa, Susumu, Kamasaki, Tomoko, Akieda, Yuki, Ishitani, Tohru, Hayashi, Takashi, Toda, Satoshi, Yokoyama, Koji, Lee, Gyu, Chol, Usami, Ippei, Inoue, Haruki, Takigawa, Ichigaku, Gauquelin, Estelle, Sugimura, Kaoru, Hino, Naoya, and Fujita, Yasuyuki

Abstract

In vertebrates, newly emerging transformed cells are often apically extruded from epithelial layers through cell competition with surrounding normal epithelial cells. However, the underlying molecular mechanism remains elusive. Here, using phospho-SILAC screening, we show that phosphorylation of AHNAK2 is elevated in normal cells neighboring RasV12 cells soon after the induction of RasV12 expression, which is mediated by calcium-dependent protein kinase C. In addition, transient upsurges of intracellular calcium, which we call calcium sparks, frequently occur in normal cells neighboring RasV12 cells, which are mediated by mechanosensitive calcium channel TRPC1 upon membrane stretching. Calcium sparks then enhance cell movements of both normal and RasV12 cells through phosphorylation of AHNAK2 and promote apical extrusion. Moreover, comparable calcium sparks positively regulate apical extrusion of RasV12-transformed cells in zebrafish larvae as well. Hence, calcium sparks play a crucial role in the elimination of transformed cells at the early phase of cell competition.

Published
2022

20. Extracellular ATP facilitates cell extrusion from epithelial layers mediated by cell competition or apoptosis

Author

00844557, 50580974, Mori, Yusuke, Shiratsuchi, Naoka, Sato, Nanami, Chaya, Azusa, Tanimura, Nobuyuki, Ishikawa, Susumu, Kato, Mugihiko, Kameda, Ikumi, Kon, Shunsuke, Haraoka, Yukinari, Ishitani, Tohru, Fujita, Yasuyuki, 00844557, 50580974, Mori, Yusuke, Shiratsuchi, Naoka, Sato, Nanami, Chaya, Azusa, Tanimura, Nobuyuki, Ishikawa, Susumu, Kato, Mugihiko, Kameda, Ikumi, Kon, Shunsuke, Haraoka, Yukinari, Ishitani, Tohru, and Fujita, Yasuyuki

Abstract

For the maintenance of epithelial homeostasis, various aberrant or dysfunctional cells are actively eliminated from epithelial layers. This cell extrusion process mainly falls into two modes: cell-competition-mediated extrusion and apoptotic extrusion. However, it is not clearly understood whether and how these processes are governed by common molecular mechanisms. In this study, we demonstrate that the reactive oxygen species (ROS) levels are elevated within a wide range of epithelial layers around extruding transformed or apoptotic cells. The downregulation of ROS suppresses the extrusion process. Furthermore, ATP is extracellularly secreted from extruding cells, which promotes the ROS level and cell extrusion. Moreover, the extracellular ATP and ROS pathways positively regulate the polarized movements of surrounding cells toward extruding cells in both cell-competition-mediated and apoptotic extrusion. Hence, extracellular ATP acts as an “extrude me” signal and plays a prevalent role in cell extrusion, thereby sustaining epithelial homeostasis and preventing pathological conditions or disorders.

Published
2022

22. Impact of RNF213 c.14576G>A Variant on the Development of Direct and Indirect Revascularization in Pediatric Moyamoya Disease.

Author

Kawabori, Masahito, Ito, Masaki, Kazumata, Ken, Tokairin, Kikutaro, Hatanaka, Kanako C., Ishikawa, Susumu, Houkin, Kiyohiro, and Fujimura, Miki

Subjects
MOYAMOYA disease, MAGNETIC resonance angiography, CHILD patients, TEMPORAL arteries, BASILAR artery
Abstract

Background: Superficial temporal artery (direct) and encephalomyosynangiosis (indirect) revascularization may develop after combined bypass surgery in pediatric patients with moyamoya disease (MMD). However, arterial development varies widely among patients, and the underlying mechanisms remain unknown. Objectives: We evaluated the relationship between the development of donor arteries after bypass surgery in pediatric patients with MMD and the MMD-susceptibility gene variant c.14576G>A of ring finger protein (RNF) 213. Methods: The data of pediatric patients with MMD (age <16 years at the time of surgery) treated with combined bypass surgery between September 2013 and April 2019 were consecutively analyzed. Quantitative measurements of the superficial temporal artery (STA), deep temporal artery (DTA), and middle meningeal artery (MMA) diameters with magnetic resonance angiography (MRA) source imaging were performed preoperatively and at 6–12 months postoperatively. The postoperative caliber change ratios (CCRs) were calculated. The relationship between CCRs and RNF213 c.14576G>A status was examined. Results: Forty-eight hemispheres from 28 pediatric patients with MMD were examined. Three hemispheres belonged to patients with the AA genotype; 33 to patients with the AG genotype (AA/AG group); and 12 to patients with the GG genotype (GG group; wild type). The CCRs for the DTA were significantly higher in patients with RNF213 variant (AA/AG group; 2.5 ± 0.1) than in the GG group (2.0 ± 0.2) (p = 0.03), whereas the CCRs for the STA were significantly higher in the GG (1.6 ± 0.1) than in the AA/AG group (1.3 ± 0.6) (p = 0.02). There was no significant difference in the CCRs for the MMA and basilar artery between the groups. Other factors, including sex, age, and MRA grading, were not associated with the development of specific bypass development. Conclusions: The extent of collateral development associated with direct or indirect bypass was found to differ between the genotypes of the RNF213 c.14576G>A associated with pediatric MMD. This genetic variant correlates with the development of the disease and affects revascularization after bypass surgery in pediatric patients with MMD. [ABSTRACT FROM AUTHOR]

Published
2023
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27. ZAK Inhibitor PLX4720 Promotes Extrusion of Transformed Cells via Cell Competition

Author

50580974, Maruyama, Takeshi, Sasaki, Ayana, Iijima, Sayuri, Ayukawa, Shiyu, Goda, Nobuhito, Tazuru, Keisuke, Hashimoto, Norikazu, Hayashi, Takashi, Kozawa, Kei, Sato, Nanami, Ishikawa, Susumu, Morita, Tomoko, Fujita, Yasuyuki, 50580974, Maruyama, Takeshi, Sasaki, Ayana, Iijima, Sayuri, Ayukawa, Shiyu, Goda, Nobuhito, Tazuru, Keisuke, Hashimoto, Norikazu, Hayashi, Takashi, Kozawa, Kei, Sato, Nanami, Ishikawa, Susumu, Morita, Tomoko, and Fujita, Yasuyuki

Abstract

Previous studies have revealed that, at the initial step of carcinogenesis, transformed cells are often eliminated from epithelia via cell competition with the surrounding normal cells. In this study, we performed cell competition-based high-throughput screening for chemical compounds using cultured epithelial cells and confocal microscopy. PLX4720 was identified as a hit compound that promoted apical extrusion of RasV12-transformed cells surrounded by normal epithelial cells. Knockdown/knockout of ZAK, a target of PLX4720, substantially enhanced the apical elimination of RasV12 cells in vitro and in vivo. ZAK negatively modulated the accumulation or activation of multiple cell competition regulators. Moreover, PLX4720 treatment promoted apical elimination of RasV12-transformed cells in vivo and suppressed the formation of potentially precancerous tumors. This is the first report demonstrating that a cell competition-promoting chemical drug facilitates apical elimination of transformed cells in vivo, providing a new dimension in cancer preventive medicine.

Published
2020

39. Daily Intake of Paraprobiotic Lactobacillus amylovorus CP1563 Improves Pre-Obese Conditions and Affects the Gut Microbial Community in Healthy Pre-Obese Subjects: A Double-Blind, Randomized, Placebo-Controlled Study

Author

Sugawara, Tomonori, primary, Sawada, Daisuke, additional, Yanagihara, Sae, additional, Aoki, Yumeko, additional, Takehara, Isao, additional, Sugahara, Hirosuke, additional, Hirota, Tatsuhiko, additional, Nakamura, Yasunori, additional, and Ishikawa, Susumu, additional

Published
2020
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40. Synthesis of Biaryls Having a Piperidylmethyl Group Based on Space Integration of Lithiation, Borylation, and Suzuki-Miyaura Coupling

Author

Takahashi, Yusuke, primary, Ashikari, Yosuke, additional, Takumi, Masahiro, additional, Shimizu, Yutaka, additional, Jiang, Yiyuan, additional, Higuma, Ryosuke, additional, Ishikawa, Susumu, additional, Sakaue, Hodaka, additional, Shite, Ibuki, additional, Maekawa, Kei, additional, Aizawa, Yoko, additional, Yamashita, Hiroki, additional, Yonekura, Yuya, additional, Colella, Marco, additional, Luisi, Renzo, additional, Takegawa, Toshihiro, additional, Fujita, Chiemi, additional, and Nagaki, Aiichiro, additional

Published
2020
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