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      암 미세환경에서 ZO 단백질의 역할 고찰 = Examining the Role of ZO Protein in the Cancer Microenvironment

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      https://www.riss.kr/link?id=A109047000

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      국문 초록 (Abstract) kakao i 다국어 번역

      Zonula occludens (ZO) 단백질은 세포 간의 접합 및 세포질 표면에서 구조적으로 기초를 제공하는 스캐폴딩 단백질로 통합 막 단백질과 세포골격 사이를 연결해주는 역할을 하며 구조적 기능 이외에도 세포 성장 및 증식 조절에도 참여를 한다. 최근 연구들에 따르면 ZO 단백질이 여러 질병 중에서도 암에 관여를 한다는 사실을 보여주고 있다. 특히, ZO 단백질은 암 미세환경에서 암세포의 성장과 발달에 영향을 주고 있다고 보고되고 있다. ZO 단백질은 혈관신생, 염증 반응, 상피-중간엽 전이, 중간엽 줄기 세포와의 상호작용을 통해 암 미세환경에서 다양한 기능을 수행한다. 이런 작용 메커니즘은 암의 종류 및 환경적 조건에 따라 달라질 수 있어 최근까지도 이와 관련된 연구들이 진행되면서 ZO 단백질이 참여하는 여러 신호전달기작들이 밝혀지고 있다. 이를 통해 암세포 환경에서 암 성장과 발달을 늦춰줄 수 있는 새로운 치료법도 고려해 볼 수 있다. 또한 ZO 단백질의 세포 및 생체 내 역할에 대한 연구는 계속되고 있지만, 신호전달 기작들이 생체 내 암 미세환경에서 어떻게 작용하는지에 대한 이해는 아직 부족하다. 따라서, 본 리뷰에서는 ZO 단백질 관련 암 미세환경의 특징 및 조절 기작을 소개하고 ZO 단백질의 특성을 활용하여 암 세포 환경을 억제하고 생체 내 ZO 단백질의 역할을 고찰하고자 한다.
      번역하기

      Zonula occludens (ZO) 단백질은 세포 간의 접합 및 세포질 표면에서 구조적으로 기초를 제공하는 스캐폴딩 단백질로 통합 막 단백질과 세포골격 사이를 연결해주는 역할을 하며 구조적 기능 이외...

      Zonula occludens (ZO) 단백질은 세포 간의 접합 및 세포질 표면에서 구조적으로 기초를 제공하는 스캐폴딩 단백질로 통합 막 단백질과 세포골격 사이를 연결해주는 역할을 하며 구조적 기능 이외에도 세포 성장 및 증식 조절에도 참여를 한다. 최근 연구들에 따르면 ZO 단백질이 여러 질병 중에서도 암에 관여를 한다는 사실을 보여주고 있다. 특히, ZO 단백질은 암 미세환경에서 암세포의 성장과 발달에 영향을 주고 있다고 보고되고 있다. ZO 단백질은 혈관신생, 염증 반응, 상피-중간엽 전이, 중간엽 줄기 세포와의 상호작용을 통해 암 미세환경에서 다양한 기능을 수행한다. 이런 작용 메커니즘은 암의 종류 및 환경적 조건에 따라 달라질 수 있어 최근까지도 이와 관련된 연구들이 진행되면서 ZO 단백질이 참여하는 여러 신호전달기작들이 밝혀지고 있다. 이를 통해 암세포 환경에서 암 성장과 발달을 늦춰줄 수 있는 새로운 치료법도 고려해 볼 수 있다. 또한 ZO 단백질의 세포 및 생체 내 역할에 대한 연구는 계속되고 있지만, 신호전달 기작들이 생체 내 암 미세환경에서 어떻게 작용하는지에 대한 이해는 아직 부족하다. 따라서, 본 리뷰에서는 ZO 단백질 관련 암 미세환경의 특징 및 조절 기작을 소개하고 ZO 단백질의 특성을 활용하여 암 세포 환경을 억제하고 생체 내 ZO 단백질의 역할을 고찰하고자 한다.

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      다국어 초록 (Multilingual Abstract) kakao i 다국어 번역

      The zonula occludens (ZO) protein serves as a scaffolding protein, providing structural support at the junctions between cells and the cytoplasmic surface. It acts as a bridge between integral membrane proteins and the cytoskeleton. Besides its structural role, it also participates in regulating cell growth and proliferation. Recent studies have highlighted the involvement of ZO protein in various diseases, including cancer. Specifically, research has indicated that ZO protein influences the cancer microenvironment surrounding cancer cells, thereby facilitating their growth and development. ZO proteins exert diverse functions in the cancer microenvironment, impacting processes such as angiogenesis, inflammatory responses, the epithelial-mesenchymal transition, and interactions with mesenchymal stem cells. The specific mechanisms vary depending on the type of cancer and environmental conditions. Recent research unveiled several signaling pathways involving ZO protein, which could potentially impede cancer progression in the tumor microenvironment. Consequently, these insights open avenues for novel treatment strategies. While the numerous physiological, structural, and morphological roles of ZO protein have been observed at the cellular and in vivo levels, understanding the signaling mechanisms it operates in vivo and how these mechanisms influence the cancer microenvironment remains a challenge. In this review, we delineate the characteristics and regulatory mechanisms of ZO protein in the context of the cancer microenvironment. Additionally, we propose leveraging the properties of ZO protein to devise defense mechanisms within the cancer cell environment and provide an overview of its in vivo role.
      번역하기

      The zonula occludens (ZO) protein serves as a scaffolding protein, providing structural support at the junctions between cells and the cytoplasmic surface. It acts as a bridge between integral membrane proteins and the cytoskeleton. Besides its struct...

      The zonula occludens (ZO) protein serves as a scaffolding protein, providing structural support at the junctions between cells and the cytoplasmic surface. It acts as a bridge between integral membrane proteins and the cytoskeleton. Besides its structural role, it also participates in regulating cell growth and proliferation. Recent studies have highlighted the involvement of ZO protein in various diseases, including cancer. Specifically, research has indicated that ZO protein influences the cancer microenvironment surrounding cancer cells, thereby facilitating their growth and development. ZO proteins exert diverse functions in the cancer microenvironment, impacting processes such as angiogenesis, inflammatory responses, the epithelial-mesenchymal transition, and interactions with mesenchymal stem cells. The specific mechanisms vary depending on the type of cancer and environmental conditions. Recent research unveiled several signaling pathways involving ZO protein, which could potentially impede cancer progression in the tumor microenvironment. Consequently, these insights open avenues for novel treatment strategies. While the numerous physiological, structural, and morphological roles of ZO protein have been observed at the cellular and in vivo levels, understanding the signaling mechanisms it operates in vivo and how these mechanisms influence the cancer microenvironment remains a challenge. In this review, we delineate the characteristics and regulatory mechanisms of ZO protein in the context of the cancer microenvironment. Additionally, we propose leveraging the properties of ZO protein to devise defense mechanisms within the cancer cell environment and provide an overview of its in vivo role.

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      참고문헌 (Reference)

      1 Chen, X. W., "microRNA-130a suppresses breast cancer cell migration and invasion by targeting FOSL1 and upregulating ZO-1" 119 : 4945-4956, 2018

      2 Lesage, J., "Zonula occludens-1/NF-κB/CXCL8 : a new regulatory axis for tumor angiogenesis" 31 : 1678-1688, 2017

      3 Lima, W. R., "ZONAB promotes proliferation and represses differentiation of proximal tubule epithelial cells" 21 : 478-488, 2010

      4 Xu, J. L., "ZO-2/Tjp2 suppresses Yap and Wwtr1/Taz-mediated hepatocyte to cholangiocyte transdifferentiation in the mouse liver" 7 : 2022

      5 Park, A., "ZO-1 regulates the migration of mesenchymal stem cells in cooperation with α-catenin in response to breast tumor cells" 10 : 2024

      6 Neyrinck-Leglantier, D., "ZO-1 intracellular localization organizes immune response in non-small cell lung cancer" 9 : 2021

      7 Haas, A. J., "ZO-1 guides tight junction assembly and epithelial morphogenesis via cytoskeletal tension-dependent and independent functions" 11 : 2022

      8 Tornavaca, O., "ZO-1 controls endothelial adherens junctions, cell-cell tension, angiogenesis, and barrier formation" 208 : 821-838, 2015

      9 Smalley, K. S. M., "Up-regulated expression of zonula occludens protein-1 in human melanoma associates with N-cadherin and contributes to invasion and adhesion" 166 : 1541-1554, 2005

      10 Baghba, R., "Tumor microenvironment complexity and therapeutic implications at a glance" 18 : 2020

      1 Chen, X. W., "microRNA-130a suppresses breast cancer cell migration and invasion by targeting FOSL1 and upregulating ZO-1" 119 : 4945-4956, 2018

      2 Lesage, J., "Zonula occludens-1/NF-κB/CXCL8 : a new regulatory axis for tumor angiogenesis" 31 : 1678-1688, 2017

      3 Lima, W. R., "ZONAB promotes proliferation and represses differentiation of proximal tubule epithelial cells" 21 : 478-488, 2010

      4 Xu, J. L., "ZO-2/Tjp2 suppresses Yap and Wwtr1/Taz-mediated hepatocyte to cholangiocyte transdifferentiation in the mouse liver" 7 : 2022

      5 Park, A., "ZO-1 regulates the migration of mesenchymal stem cells in cooperation with α-catenin in response to breast tumor cells" 10 : 2024

      6 Neyrinck-Leglantier, D., "ZO-1 intracellular localization organizes immune response in non-small cell lung cancer" 9 : 2021

      7 Haas, A. J., "ZO-1 guides tight junction assembly and epithelial morphogenesis via cytoskeletal tension-dependent and independent functions" 11 : 2022

      8 Tornavaca, O., "ZO-1 controls endothelial adherens junctions, cell-cell tension, angiogenesis, and barrier formation" 208 : 821-838, 2015

      9 Smalley, K. S. M., "Up-regulated expression of zonula occludens protein-1 in human melanoma associates with N-cadherin and contributes to invasion and adhesion" 166 : 1541-1554, 2005

      10 Baghba, R., "Tumor microenvironment complexity and therapeutic implications at a glance" 18 : 2020

      11 Landy, J., "Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer" 22 : 3117-3126, 2016

      12 Ellaine, S., "Tight Junctions and the tumor microenvironment" 4 : 135-145, 2016

      13 de Visser, K. E., "The evolving tumor microenvironment From cancer initiation to metastatic outgrowth" 41 : 374-403, 2023

      14 Balda, M. S., "The ZO-1-associated Y-box factor ZONAB regulates epithelial cell proliferation and cell density" 160 : 423-432, 2003

      15 Lee, T. J., "The PDZ motif peptide of ZO-1 attenuates Pseudomonas aeruginosa LPS-induced airway inflammation" 10 : 2020

      16 Reichert, M., "The PDZ domains of zonula occludens-1 induce an epithelial to mesenchymal transition of Madin-Darby canine kidney I cells- : Evidence for a role of β-catenin/Tcf/Lef signaling" 275 : 9492-9500, 2000

      17 Ram, A. K., "Role of zonula occludens in gastrointestinal and liver cancers" 10 : 3647-3661, 2022

      18 Chen, Y., "Regulation of ZO-1 on β-catenin mediates sulforaphane suppressed colorectal cancer stem cell properties in colorectal cancer" 13 : 12363-12370, 2022

      19 Wu, J., "RBM38 is involved in TGF-β-induced epithelial-to-mesenchymal transition by stabilising zonula occludens-1 mRNA in breast cancer" 117 : 675-684, 2017

      20 Ghosh, D., "PLP2 drives collective cell migration via ZO-1-mediated cytoskeletal remodeling at the leading edge in human colorectal cancer cells" 134 : 2021

      21 Ibrahim, S., "PIK3R3 regulates ZO-1 expression through the NF-kB pathway in inflammatory bowel disease" 85 : 2020

      22 Christensen, N. R., "PDZ domains as drug targets" 2 : 10-, 2019

      23 Han Seo ; Hyun-Chae Lee ; Ki Chul Lee ; Doosik Kim ; Jiwook Kim ; Donghee Kang ; Hyung-Joo Chung ; Hee-Jae Cha ; Jeongtae Kim ; 송경섭, "PDZ Peptide of the ZO-1 protein significantly increases UTP-Induced MUC8 anti-inflammatory mucin overproduction in human airway epithelial cells" 46 : 700-709, 2023

      24 Hu, S. L., "Mesenchymal stem cell microvesicles restore protein permeability across primary cultures of injured human lung microvascular endothelial cells" 7 : 615-624, 2018

      25 Martin, T. A., "Loss of tight junction plaque molecules in breast cancer tissues is associated with a poor prognosis in patients with breast cancer" 40 : 2717-2725, 2004

      26 이성희, "Intestinal Permeability Regulation by Tight Junction : Implication on Inflammatory Bowel Diseases" 13 : 11-18, 2015

      27 Ram, A. K., "Increased systemic zonula occludens 1 associated with inflammation and independent biomarker in patients with hepatocellular carcinoma" 18 : 2018

      28 Mauro, L., "IGF-I receptor-induced cell-cell adhesion of MCF-7 breast cancer cells requires the expression of junction protein ZO-1" 276 : 39892-39897, 2001

      29 Lee, Y. C., "High expression of tight junction protein 1 as a predictive biomarker for bladder cancer grade and staging" 12 : 2022

      30 Kim, H. S., "GNAQ-regulated ZO-1and ZO-2 act as tumor suppressors by modulating EMT potential and tumor-repressive microenvironment in lung cancer" 24 : 2023

      31 Ko, E. J., "Functional analysis of membrane-associated scaffolding tight junction(TJ)proteins in tumorigenic characteristics of B16-F10 mouse melanoma cells" 25 : 2024

      32 Chen, B. B., "Expression of tight junction proteins Is altered in bladder cancer" 2020 : 10-, 2020

      33 Luo, Y. H., "Effects of resveratrol on tight junction proteins and the Notch1 pathway in an HT-29 cell model of inflammation Induced by Lipopolysaccharide" 45 : 2449-2464, 2022

      34 Utepbergenov, D. I., "Dimerization of the scaffolding protein ZO-1 through the second PDZ domain" 281 : 24671-24677, 2006

      35 Hue, C. D., "Dexamethasone potentiates in vitro blood-brain barrier recovery after primary blast injury by glucocorticoid receptor-mediated upregulation of ZO-1 tight junction protein" 35 : 1191-1198, 2015

      36 Zhang, X. L., "Decreased expression of ZO-1 is associated with tumor metastases in liver cancer" 17 : 1859-1864, 2019

      37 Shuying Tian ; Ruixue Guo ; Sichen Wei ; Yu Kong ; Xinliang Wei ; Weiwei Wang ; Xiaomeng Shi ; Hongyu Jiang, "Curcumin protects against the intestinal ischemia-reperfusion injury : involvement of the tight junction protein ZO-1 and TNF-αrelated mechanism" 20 : 147-152, 2016

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