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2 results on '"Noriko Yasuda"'

1. Inflammation-driven senescence-associated secretory phenotype in cancer-associated fibroblasts enhances peritoneal dissemination

Author

Tadahito Yasuda, Mayu Koiwa, Atsuko Yonemura, Keisuke Miyake, Ryusho Kariya, Sho Kubota, Takako Yokomizo-Nakano, Noriko Yasuda-Yoshihara, Tomoyuki Uchihara, Rumi Itoyama, Luke Bu, Lingfeng Fu, Kota Arima, Daisuke Izumi, Shiro Iwagami, Kojiro Eto, Masaaki Iwatsuki, Yoshifumi Baba, Naoya Yoshida, Hiroto Ohguchi, Seiji Okada, Keisuke Matsusaki, Goro Sashida, Akiko Takahashi, Patrick Tan, Hideo Baba, and Takatsugu Ishimoto

Subjects
cancer-associated fibroblasts, senescence-associated secretory phenotype, EZH2, gastric cancer, peritoneal dissemination, H3K27me3 marks, Biology (General), QH301-705.5
Abstract

Summary: In the tumor microenvironment, senescent non-malignant cells, including cancer-associated fibroblasts (CAFs), exhibit a secretory profile under stress conditions; this senescence-associated secretory phenotype (SASP) leads to cancer progression and chemoresistance. However, the role of senescent CAFs in metastatic lesions and the molecular mechanism of inflammation-related SASP induction are not well understood. We show that pro-inflammatory cytokine-driven EZH2 downregulation maintains the SASP by demethylating H3K27me3 marks in CAFs and enhances peritoneal tumor formation of gastric cancer (GC) through JAK/STAT3 signaling in a mouse model. A JAK/STAT3 inhibitor blocks the increase in GC cell viability induced by senescent CAFs and peritoneal tumor formation. Single-cell mass cytometry revealed that fibroblasts exist in the ascites of GC patients with peritoneal dissemination, and the fibroblast population shows p16 expression and SASP factors at high levels. These findings provide insights into the inflammation-related SASP maintenance by histone modification and the role of senescent CAFs in GC peritoneal dissemination.

Published
2021
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2. Inflammation-driven senescence-associated secretory phenotype in cancer-associated fibroblasts enhances peritoneal dissemination

Author

Kojiro Eto, Takako Yokomizo-Nakano, Seiji Okada, Noriko Yasuda-Yoshihara, Daisuke Izumi, Lingfeng Fu, Hiroto Ohguchi, Luke Bu, Sho Kubota, Patrick Tan, Mayu Koiwa, Keisuke Miyake, Rumi Itoyama, Ryusho Kariya, Yoshifumi Baba, Goro Sashida, Tadahito Yasuda, Keisuke Matsusaki, Kota Arima, Akiko Takahashi, Tomoyuki Uchihara, Atsuko Yonemura, Masaaki Iwatsuki, Hideo Baba, Naoya Yoshida, Shiro Iwagami, and Takatsugu Ishimoto

Subjects
0301 basic medicine, Male, Pyridines, 0302 clinical medicine, Tumor Microenvironment, lcsh:QH301-705.5, Peritoneal Neoplasms, education.field_of_study, Mice, Inbred BALB C, EZH2, peritoneal dissemination, Middle Aged, Tyrphostins, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, senescence-associated secretory phenotype, Cytokines, Female, Inflammation Mediators, cancer-associated fibroblasts, Signal Transduction, STAT3 Transcription Factor, Population, Mice, Nude, Antineoplastic Agents, Biology, General Biochemistry, Genetics and Molecular Biology, H3K27me3 marks, 03 medical and health sciences, Downregulation and upregulation, Stomach Neoplasms, Cell Line, Tumor, medicine, Animals, Humans, Janus Kinase Inhibitors, Enhancer of Zeste Homolog 2 Protein, Viability assay, education, Fibroblast, Aged, Janus Kinases, Tumor microenvironment, gastric cancer, fungi, Cancer, medicine.disease, Xenograft Model Antitumor Assays, 030104 developmental biology, lcsh:Biology (General), Cancer research, Cancer-Associated Fibroblasts, 030217 neurology & neurosurgery
Abstract

Summary: In the tumor microenvironment, senescent non-malignant cells, including cancer-associated fibroblasts (CAFs), exhibit a secretory profile under stress conditions; this senescence-associated secretory phenotype (SASP) leads to cancer progression and chemoresistance. However, the role of senescent CAFs in metastatic lesions and the molecular mechanism of inflammation-related SASP induction are not well understood. We show that pro-inflammatory cytokine-driven EZH2 downregulation maintains the SASP by demethylating H3K27me3 marks in CAFs and enhances peritoneal tumor formation of gastric cancer (GC) through JAK/STAT3 signaling in a mouse model. A JAK/STAT3 inhibitor blocks the increase in GC cell viability induced by senescent CAFs and peritoneal tumor formation. Single-cell mass cytometry revealed that fibroblasts exist in the ascites of GC patients with peritoneal dissemination, and the fibroblast population shows p16 expression and SASP factors at high levels. These findings provide insights into the inflammation-related SASP maintenance by histone modification and the role of senescent CAFs in GC peritoneal dissemination.

Published
2021

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