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45 results on '"Yoshida, Saishu"'

3. Extended-Synaptotagmin 1 Enhances Liver Cancer Progression Mediated by the Unconventional Secretion of Cytosolic Proteins

Author

Yamada, Kohji, primary, Hannya, Yoshito, additional, Oikawa, Tsunekazu, additional, Yoshida, Ayano, additional, Katagiri, Kuniko, additional, Yoshida, Saishu, additional, Koizumi, Rei, additional, Tago, Naoko, additional, Shimoyama, Yuya, additional, Kawamura, Akira, additional, Mochimaru, Yuta, additional, Eto, Ken, additional, and Yoshida, Kiyotsugu, additional

Published
2023
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7. Extended-synaptotagmin 1 engages in unconventional protein secretion mediated via SEC22B+vesicle pathway in liver cancer

Author

Yamada, Kohji, primary, Motohashi, Saya, additional, Oikawa, Tsunekazu, additional, Tago, Naoko, additional, Koizumi, Rei, additional, Ono, Masaya, additional, Tachibana, Toshiaki, additional, Yoshida, Ayano, additional, Yoshida, Saishu, additional, Shimoda, Masayuki, additional, Oka, Masahiro, additional, Yoneda, Yoshihiro, additional, and Yoshida, Kiyotsugu, additional

Published
2022
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16. Unconventional Secretion of PKCδ Exerts Tumorigenic Function via Stimulation of ERK1/2 Signaling in Liver Cancer

Author

Yamada, Kohji, primary, Oikawa, Tsunekazu, additional, Kizawa, Ryusuke, additional, Motohashi, Saya, additional, Yoshida, Saishu, additional, Kumamoto, Tomotaka, additional, Saeki, Chisato, additional, Nakagawa, Chika, additional, Shimoyama, Yuya, additional, Aoki, Katsuhiko, additional, Tachibana, Toshiaki, additional, Saruta, Masayuki, additional, Ono, Masaya, additional, and Yoshida, Kiyotsugu, additional

Published
2021
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17. Enforced dual‐specificity tyrosine‐regulated kinase 2 expression by adenovirus‐mediated gene transfer inhibits tumor growth and metastasis of colorectal cancer.

Author

Imaizumi, Yuta, Yoshida, Saishu, Kanegae, Yumi, Eto, Ken, and Yoshida, Kiyotsugu

Abstract

Colorectal cancer is one of the most common gastrointestinal tumors with good outcomes; however, with distant metastasis, the outcomes are poor. Novel treatment methods are urgently needed. Our in vitro studies indicate that dual‐specificity tyrosine‐regulated kinase 2 (DYRK2) functions as a tumor suppressor in colorectal cancer by regulating cell survival, proliferation, and apoptosis induction. In addition, DYRK2 expression is decreased in tumor tissues compared to nontumor tissues in colorectal cancer, indicating a correlation with clinical prognosis. In this context, we devised a novel therapeutic strategy to overexpress DYRK2 in tumors by adenovirus‐mediated gene transfer. The present study shows that overexpression of DYRK2 in colon cancer cell lines by adenovirus inhibits cell proliferation and induces apoptosis in vitro. Furthermore, in mouse subcutaneous xenograft and liver metastasis models, enforced expression of DYRK2 by direct or intravenous injection of adenovirus to the tumor significantly inhibits tumor growth. Taken together, these findings show that adenovirus‐based overexpression of DYRK2 could be a novel gene therapy for liver metastasis of colorectal cancer. [ABSTRACT FROM AUTHOR]

Published
2022
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23. Involvement of DNA methylation in regulating rat Prop1 gene expression during pituitary organogenesis

Author

NISHIHARA, Hiroto, YOSHIDA, Saishu, KANNO, Naoko, NISHIMURA, Naoto, UEHARU, Hiroki, OHGANE, Jun, KATO, Takako, and KATO, Yukio

Subjects
Homeodomain Proteins, Male, endocrine system, DNA methylation, Organogenesis, Gene Expression Profiling, Temperature, Computational Biology, Gene Expression Regulation, Developmental, DNA, Epigenesis, Genetic, Rats, Pituitary, Liver, Pituitary Gland, Rat, Animals, Original Article, CpG Islands, Female, Rats, Wistar, PROP1
Abstract

PROP1 is a pituitary specific transcription factor that plays a crucial role in pituitary organogenesis. The Prop1 shows varied expression patterns that promptly emerge and then fade during the early embryonic period. However, the regulatory mechanisms governing Prop1 expression remain unclear. Here, we investigated whether Prop1 was under epigenetic regulation by DNA methylation. Bisulfite sequencing was performed on DNA obtained from the pituitary glands and livers of rats on embryonic days (E) 13.5 and E14.5, and postnatal days (P) 4 and P30. The methylation of CpG sites in seven regions from 3-kb upstream of the Prop1 transcription start site through to its second intron were examined. Certain differences in CpG-methylation levels were observed in Region-1 (-2772 b to -2355 b), Region-4 (-198 b to +286 b), Region-5 (+671 b to +990 b), and Region-6 (+1113 b to +1273 b) based on comparisons between pituitary and liver DNA on E13.5. DNA methylation in pituitary glands on E14.5, P4, and P30 was generally similar to that observed in in the pituitary gland on E13.5, whereas the anterior and intermediate lobes of the pituitary gland on P4 and P30 showed only small differences. These results indicate that Prop1 is under regulation by CpG methylation during the early period of pituitary primordium development around E13.5.

Published
2016

40. Detection of Human Herpesviruses (HHVs) in Semen of Human Male Infertile Patients

Author

CHEN, Mo, primary, CAI, Li-Yi, additional, KANNO, Naoko, additional, KATO, Takako, additional, LU, Jinxing, additional, JIN, Fan, additional, WANG, Honghua, additional, SEKITA, Masayo, additional, HIGUCHI, Masashi, additional, YOSHIDA, Saishu, additional, YAKO, Hideji, additional, UEHARU, Hiroki, additional, IZUMI, Shun-Ichiro, additional, and KATO, Yukio, additional

Published
2013
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43. Three-dimensional cell culture using CD9-positive cells isolated from marginal cell layer of intermediate lobe of rats sustains in vivo-like primary niche environment.

Author

Horiguchi K, Tsukada T, Yoshida S, Fujiwara K, Nakakura T, Azuma M, Shindo A, Hasegawa R, and Takigami S

Subjects
Animals, Rats, Pituitary Gland, Anterior metabolism, Pituitary Gland, Anterior cytology, Male, Cell Culture Techniques, Three Dimensional methods, Cells, Cultured, Proteoglycans metabolism, Laminin metabolism, Collagen, Drug Combinations, Tetraspanin 29 metabolism, Cell Differentiation, Stem Cell Niche, SOXB1 Transcription Factors metabolism
Abstract

The adenohypophysis is composed of the anterior and intermediate lobes (AL and IL, respectively), and secretes hormones that play an important role in reproduction. CD9- and SOX2-double (CD9/SOX2) positive cells located in the marginal cell layer (MCL) facing the Rathke's cleft in the AL and IL form the primary stem cell niche in the adult adenohypophysis of rats. In this study, we successfully obtained 3-dimensional (3D) cell aggregates that closely resembled the primary niche of MCL in vivo. After incubation in a Matrigel containing several growth factors, approximately 20% of the cells in the CD9/SOX2-positive cell aggregates were differentiated into hormone-producing cells. The cell aggregates generated in this study may provide insight into the regulation of the pituitary stem/progenitor cell niche and the turnover of hormone-producing cells.

Published
2024
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44. Positive regulation of Hedgehog signaling via phosphorylation of GLI2/GLI3 by DYRK2 kinase.

Author

Yoshida S, Kawamura A, Aoki K, Wiriyasermkul P, Sugimoto S, Tomiyoshi J, Tajima A, Ishida Y, Katoh Y, Tsukada T, Tsuneoka Y, Yamada K, Nagamori S, Nakayama K, and Yoshida K

Subjects
Animals, Phosphorylation, Mice, Humans, Nerve Tissue Proteins metabolism, Nerve Tissue Proteins genetics, Kruppel-Like Transcription Factors metabolism, Kruppel-Like Transcription Factors genetics, Cell Proliferation, Cilia metabolism, Smoothened Receptor metabolism, Smoothened Receptor genetics, Nuclear Proteins, Repressor Proteins, Zinc Finger Protein Gli3 metabolism, Zinc Finger Protein Gli3 genetics, Zinc Finger Protein Gli2 metabolism, Zinc Finger Protein Gli2 genetics, Protein Serine-Threonine Kinases metabolism, Protein Serine-Threonine Kinases genetics, Dyrk Kinases, Hedgehog Proteins metabolism, Hedgehog Proteins genetics, Signal Transduction, Protein-Tyrosine Kinases metabolism, Protein-Tyrosine Kinases genetics
Abstract

Hedgehog (Hh) signaling, an evolutionarily conserved pathway, plays an essential role in development and tumorigenesis, making it a promising drug target. Multiple negative regulators are known to govern Hh signaling; however, how activated Smoothened (SMO) participates in the activation of downstream GLI2 and GLI3 remains unclear. Herein, we identified the ciliary kinase DYRK2 as a positive regulator of the GLI2 and GLI3 transcription factors for Hh signaling. Transcriptome and interactome analyses demonstrated that DYRK2 phosphorylates GLI2 and GLI3 on evolutionarily conserved serine residues at the ciliary base, in response to activation of the Hh pathway. This phosphorylation induces the dissociation of GLI2/GLI3 from suppressor, SUFU, and their translocation into the nucleus. Loss of Dyrk2 in mice causes skeletal malformation, but neural tube development remains normal. Notably, DYRK2-mediated phosphorylation orchestrates limb development by controlling cell proliferation. Taken together, the ciliary kinase DYRK2 governs the activation of Hh signaling through the regulation of two processes: phosphorylation of GLI2 and GLI3 downstream of SMO and cilia formation. Thus, our findings of a unique regulatory mechanism of Hh signaling expand understanding of the control of Hh-associated diseases., Competing Interests: Competing interests statement:The authors declare no competing interest.

Published
2024
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45. Extended-synaptotagmin 1 engages in unconventional protein secretion mediated via SEC22B + vesicle pathway in liver cancer.

Author

Yamada K, Motohashi S, Oikawa T, Tago N, Koizumi R, Ono M, Tachibana T, Yoshida A, Yoshida S, Shimoda M, Oka M, Yoneda Y, and Yoshida K

Subjects
Cell Membrane metabolism, Endoplasmic Reticulum metabolism, Humans, Protein Transport, Tumor Microenvironment, Liver Neoplasms genetics, Liver Neoplasms metabolism, R-SNARE Proteins metabolism, Synaptotagmin I metabolism
Abstract

Protein secretion in cancer cells defines tumor survival and progression by orchestrating the microenvironment. Studies suggest the occurrence of active secretion of cytosolic proteins in liver cancer and their involvement in tumorigenesis. Here, we investigated the identification of extended-synaptotagmin 1 (E-Syt1), an endoplasmic reticulum (ER)-bound protein, as a key mediator for cytosolic protein secretion at the ER-plasma membrane (PM) contact sites. Cytosolic proteins interacted with E-Syt1 on the ER, and then localized spatially inside SEC22B + vesicles of liver cancer cells. Consequently, SEC22B on the vesicle tethered to the PM via Q-SNAREs (SNAP23, SNX3, and SNX4) for their secretion. Furthermore, inhibiting the interaction of protein kinase Cδ (PKCδ), a liver cancer-specific secretory cytosolic protein, with E-Syt1 by a PKCδ antibody, decreased in both PKCδ secretion and tumorigenicity. Results reveal the role of ER-PM contact sites in cytosolic protein secretion and provide a basis for ER-targeting therapy for liver cancer.

Published
2022
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