Review
Biochemistry & Molecular Biology
Rina Fujiwara-Tani, Shiori Mori, Ruiko Ogata, Rika Sasaki, Ayaka Ikemoto, Shingo Kishi, Masuo Kondoh, Hiroki Kuniyasu
Summary: CLDN4 is a crucial component of tight junctions in epithelial cells and is overexpressed in many epithelial malignancies. Changes in CLDN4 expression are associated with epigenetic factors, inflammation, and growth factor signaling. CLDN4 plays a role in maintaining the tumor microenvironment and acts as a barrier to anticancer drug entry.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Fumisato Maesaka, Masaomi Kuwada, Shohei Horii, Shingo Kishi, Rina Fujiwara-Tani, Shiori Mori, Kiyomu Fujii, Takuya Mori, Hitoshi Ohmori, Takuya Owari, Makito Miyake, Yasushi Nakai, Nobumichi Tanaka, Ujjal Kumar Bhawal, Yi Luo, Masuo Kondoh, Kiyohide Fujimoto, Hiroki Kuniyasu
Summary: In bladder urothelial carcinoma (BUC), the overexpression of CLDN4 is associated with cancer progression. Through analyzing BUC cases, it was found that hypomethylation of CLDN4 promoter DNA increases CLDN4 expression and promotes cell proliferation, stemness, and epithelial-mesenchymal transition. Treatment with demethylating agent AZA leads to excessive CLDN4 expression, specifically the TJ-unintegrated CLDN4 monomer. The TJ-unintegrated CLDN4 binds to integrin beta 1 and enhances stemness, drug resistance, and metastatic ability of the cells, as well as exhibits an anti-apoptosis effect via FAK phosphorylation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Natascha Roehlen, Marion Muller, Zeina Nehme, Emilie Crouchet, Frank Juhling, Fabio Del Zompo, Sara Cherradi, Francois H. T. Duong, Nuno Almeida, Antonio Saviano, Mirian Fernandez-Vaquero, Tobias Riedl, Houssein El Saghire, Sarah C. Durand, Clara Ponsolles, Marine A. Oudot, Romain Martin, Nicolas Brignon, Emanuele Felli, Patrick Pessaux, Antonin Lallement, Irwin Davidson, Simonetta Bandiera, Christine Thumann, Patrice Marchand, Solange Moll, Brandon Nicolay, Nabeel Bardeesy, Yujin Hoshida, Mathias Heikenwaelder, Roberto Iacone, Alberto Toso, Markus Meyer, Greg Elson, Tamas Schweighoffer, Geoffrey Teixeira, Mirjam B. Zeisel, Patrice Laquerriere, Joachim Lupberger, Catherine Schuster, Laurent Mailly, Thomas F. Baumert
Summary: In this study, the role of CLDN1 as a therapeutic target for hepatocellular carcinoma (HCC) was investigated using humanized monoclonal antibodies targeting non-junctional CLDN1 and various cell and animal models. The results demonstrated that targeting non-junctional CLDN1 significantly suppressed tumor growth and invasion, and affected tumor stemness, metabolism, oncogenic signaling, and the tumor immune microenvironment. These findings provide a rationale for targeting CLDN1 in the treatment of advanced HCC and lay the foundation for the development of CLDN1-specific monoclonal antibodies for clinical use.
JOURNAL OF HEPATOLOGY
(2023)
Article
Food Science & Technology
Yunika Mayangsari, Mayu Okudaira, Chinatsu Mano, Yuki Tanaka, Osamu Ueda, Tomohiro Sakuta, Yoshiharu Suzuki, Yoshinari Yamamoto, Takuya Suzuki
Summary: Research showed that DMF can enhance intestinal TJ barrier integrity by increasing the expression of occludin and claudin-1, while reducing the expression of claudin-2. This regulation involves the induction of occludin protein translation via mTOR and silencing Cldn2 mRNA via miR-16-5p.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Oncology
Yuta Endo, Kotaro Sugimoto, Makoto Kobayashi, Yasuyuki Kobayashi, Manabu Kojima, Shigenori Furukawa, Shu Soeda, Takafumi Watanabe, Atsuko Y. Higashi, Tomohito Higashi, Yuko Hashimoto, Keiya Fujimori, Hideki Chiba
Summary: The study evaluated the expression of CLDN9 in endometrial cancer and its association with prognosis. The results showed that high expression of CLDN9 was associated with poor prognosis and could be used in combination with CLDN6 to improve predictive sensitivity.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Kenta Shigetomi, Yumiko Ono, Kenji Matsuzawa, Junichi Ikenouchi
Summary: It has been found that cholesterol accumulation is essential for the formation of tight junctions, which are crucial for the epithelial barrier. Despite the absence of tight junctions, cholesterol still accumulates normally in the vicinity of the apical junctions. Moreover, a claudin mutant that cannot bind to Zonula Occludens (ZO) proteins can still form tight junction strands. ZO proteins are not only scaffolds for claudins, but also promote the formation of cholesterol-rich membrane domains at apical junctions through their effect on the junctional actomyosin cytoskeleton.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Abidur Rahman, Makoto Kobayashi, Kotaro Sugimoto, Yuta Endo, Manabu Kojima, Shigenori Furukawa, Takafumi Watanabe, Shu Soeda, Yuko Hashimoto, Keiya Fujimori, Hideki Chiba
Summary: The study revealed that low CLDN12 expression is associated with poor prognosis in cervical cancer, and the novel anti-CLDN12 mAb could serve as a valuable tool for assessing the biological relevance of CLDN12 expression in different cancer types and other diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Jie Chai, Xiangli Liu, Xinju Hu, Chunfang Wang
Summary: The study aimed to investigate the relationship between peripheral blood circulating tumor cells (CTCs) and Claudin-4 expression in breast cancer patients, as well as their potential impact on clinical prognosis and risk assessment. CTCs were classified and enumerated using CTC-enriched in situ hybridization, and Claudin-4 expression was detected by immunohistochemistry. Higher Claudin-4 expression was associated with increased CTC counts, especially of mesenchymal CTCs (M-CTCs), and was an independent predictor of poor prognosis in breast cancer patients. The findings suggest the importance of considering CTCs and Claudin-4 expression for risk assessment and prognosis in breast cancer patients.
PATHOLOGY & ONCOLOGY RESEARCH
(2023)
Article
Oncology
Yuko Murakami-Nishimagi, Kotaro Sugimoto, Makoto Kobayashi, Kazunoshin Tachibana, Manabu Kojima, Maiko Okano, Yuko Hashimoto, Shigehira Saji, Tohru Ohtake, Hideki Chiba
Summary: Cell adhesion signaling through CLDN4 accelerates breast cancer progression by promoting cell metabolism and activation of AKT pathway; the specific mechanisms involve the activation of Src-family kinases and phosphorylation of LXR beta.
BREAST CANCER RESEARCH
(2023)
Article
Cell Biology
Hyunjhung Jhun, Won-Young Lee, Jin-Ki Park, Sun-Goo Hwang, Hyun-Jung Park
Summary: Cryptorchidism may affect Claudin expression, which in turn impacts the proliferation of Sertoli cells and spermatogenesis.
Article
Biochemistry & Molecular Biology
Abigail Taylor, Mark Warner, Christopher Mendoza, Calvin Memmott, Tom LeCheminant, Sara Bailey, Colter Christensen, Julie Keller, Arminda Suli, Dario Mizrachi
Summary: The tight junction (TJ) is a structure composed of multiple proteins responsible for cell-cell adhesion in polarized endothelium and epithelium. This article introduces a new experimental method to study the membrane protein claudins (CLDNs), providing a novel approach for studying other membrane proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Harleen Kaur, Regis Moreau
Summary: The role of mTORC1 in the regulation of intestinal barrier function and permeability remains to be fully elucidated.
Article
Multidisciplinary Sciences
Alex J. Vecchio, Sewwandi S. Rathnayake, Robert M. Stroud
Summary: The study reveals the molecular and structural basis of how CpE targets susceptible claudins, as well as differences in the primary CpE receptors in mice and humans due to sequence changes in the target motif.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Caroline Hempel, Rita Rosenthal, Anja Fromm, Susanne M. Krug, Michael Fromm, Dorothee Gunzel, Joerg Piontek
Summary: This study analyzed the structural and functional differences between claudin-15 and claudin-10b cation channels and identified several mutants that affect ion permeability and pore diameter. Furthermore, the study revealed that the charge at the W63/K64 position has an impact on the assembly and properties of claudin-10b channels but not claudin-15 channels.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Review
Multidisciplinary Sciences
Erika Wakayama, Taiki Kuzu, Keisuke Tachibana, Ryuichi Hirayama, Yoshiaki Okada, Masuo Kondoh
Summary: The blood-brain barrier poses a challenge to drug delivery to the central nervous system. Among the components of the tight junctions in the blood-brain barrier, claudin-5 has been studied extensively as a target for enhancing drug permeation into the brain. However, sustained knockdown of claudin-5 is lethal in mice and administration of an anti-claudin-5 antibody can cause convulsions in nonhuman primates.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)