Article
Oncology
Jordi Gonzalez-Molina, Paula Hahn, Raul Maia Falcao, Okan Gultekin, Georgia Kokaraki, Valentina Zanfagnin, Tirzah Braz Petta, Kaisa Lehti, Joseph W. W. Carlson
Summary: This study explored the impact of fibrillar collagens on uterine leiomyosarcoma (uLMS) and found that uLMS tumors have low collagen density and increased expression of collagen-remodeling genes compared to uterine leiomyomas (LM)．The overexpression of matrix metalloproteinase-14 (MMP14) in uLMS was found to support uLMS cell proliferation, and uLMS cells were found to be less sensitive to changes in collagen substrate stiffness. Additionally, enhanced basal yes-associated protein 1 (YAP) activity was observed in uLMS cells, which sustains their growth in low-stiffness substrates. These findings suggest that matrix remodeling and YAP may be potential therapeutic targets for uLMS．
MOLECULAR ONCOLOGY
(2023)
Article
Orthopedics
H. Meng, S. Fu, M. B. Ferreira, Y. Hou, O. M. Pearce, N. Gavara, M. M. Knight
Summary: The objective of this study was to clarify the role of YAP in modulating cartilage inflammation and degradation, and the involvement of primary cilia and associated intraflagellar transport (IFT). The researchers cultured isolated primary chondrocytes on substrates of different stiffness or treated them with YAP agonist LPA or YAP antagonist VP. They also genetically modified the chondrocytes and monitored the IL1β response by measuring the release of nitric oxide (NO) and prostaglandin E2 (PGE2). The mechanical properties of cartilage explants were tested to confirm cartilage degradation, and the involvement of primary cilia and IFT was analyzed.
OSTEOARTHRITIS AND CARTILAGE
(2023)
Article
Biochemistry & Molecular Biology
Jingwei Cai, Tianyi Chen, Zhiyu Jiang, Jiafei Yan, Zhengtao Ye, Yeling Ruan, Liye Tao, Zefeng Shen, Xiao Liang, Yifan Wang, Junjie Xu, Xiujun Cai
Summary: Studies have shown that matrix stiffness plays a role in the development of hepatocellular carcinoma (HCC). By analyzing the TCGA-LIHC database and GEO datasets, researchers identified three distinct metabolic subtypes in HCC with different prognoses and features. They found that long-chain acyl-CoA dehydrogenase (ACADL) is a mechanoreactive enzyme that regulates lipid metabolism in HCC cells in response to matrix stiffness. The study also revealed that the YAP/TEAD4 transcriptional complex regulates ACADL expression in HCC cells.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Cell Biology
Yuanyuan Fu, Pengzhi Wan, Jie Zhang, Xue Li, Jia Xing, Yu Zou, Kaiyue Wang, Hui Peng, Qizhuo Zhu, Liu Cao, Xiaoyue Zhai
Summary: It was found in the study that increased ECM stiffness aggravates the progression of renal fibrosis through the Piezo1-p38MAPK-YAP pathway, and targeting mechanosensitive Piezo1 might be a potential therapeutic strategy for delaying the progression of renal fibrosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Yue Li, Fan Li, Xiaoyu Bai, Yanlei Li, Chunsheng Ni, Xiulan Zhao, Danfang Zhang
Summary: The study identified ITGA3 as a novel biomarker for estimating the diagnosis and prognosis of breast cancer, and revealed its involvement in ECM regulation and immune cell infiltration.
FRONTIERS IN ONCOLOGY
(2021)
Article
Engineering, Biomedical
Yaru Guo, Feng Mei, Ying Huang, Siqin Ma, Yan Wei, Xuehui Zhang, Mingming Xu, Ying He, Boon Chin Heng, Lili Chen, Xuliang Deng
Summary: This study demonstrates that matrix stiffness promotes sprouting of endothelial cells and regulates the formation of tip cells through a specific signaling axis. The findings have significant implications for biomaterial design and treatment of pathological conditions.
BIOACTIVE MATERIALS
(2022)
Article
Cell Biology
Xianliang Gu, Lingling Ge, Bangqi Ren, Yajie Fang, Yijian Li, Yi Wang, Haiwei Xu
Summary: This study identified the mechanism by which glucocorticoids activate YAP and promote ECM remodeling in retinal capillary endothelial cells, providing new insights into the early pathogenesis of diabetic retinopathy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Valeriya Pankova, Khin Thway, Robin L. Jones, Paul H. Huang
Summary: Soft tissue sarcomas are rare cancers of mesenchymal origin that produce large quantities of extracellular matrix components, which play a key role in sarcomagenesis through interactions with cell adhesion receptors. Studies have identified key ECM components and their important role in sarcomagenesis, highlighting the need for more comprehensive analyses to identify new drug targets and prognostic biomarkers.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Yu Shen, Dian Jing, Zhihe Zhao
Summary: Extracellular matrix (ECM) stiffness plays a crucial role in the differentiation of human bone marrow mesenchymal stem cells (hBMSCs). This study reveals that the phosphoinositide 3-kinase (PI3K)-AKT pathway is highly correlated with ECM stiffness. AKT phosphorylation influences the subcellular localization and activation of Yes-associated protein (YAP).
CELLULAR SIGNALLING
(2022)
Article
Oncology
Jianming Tang, Xiaoli Tian, Jie Min, Ming Hu, Li Hong
Summary: The upregulation of RPP40 is significantly correlated with poor prognosis and the tumor microenvironment in uterine corpus endometrial carcinoma (UCEC), suggesting that RPP40 may serve as a promising biomarker and potential target for chemotherapy or immunotherapy in UCEC.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Esther Marhuenda, Alvaro Villarino, Maria Leonor Narciso, Marta Camprubi-Rimblas, Ramon Farre, Nuria Gavara, Antonio Artigas, Isaac Almendros, Jorge Otero
Summary: One of the main limitations in in vitro studies on lung diseases is maintaining the specific phenotype of alveolar epithelial cells. This study successfully maintained the phenotype of cells using lung-derived extracellular matrix hydrogels, and found that the hydrogels can promote long-term culture of alveolar epithelial cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Jingxiao Du, Tianwei Qian, Yi Lu, Wenkai Zhou, Xun Xu, Chaoyang Zhang, Jingfa Zhang, Zhihua Zhang
Summary: This study explored the potential role and mechanism of SPARC in promoting fibrosis. The results showed that exogenous SPARC induced the transformation of human Tenon's fibroblasts into myofibroblasts by activating the YAP/TAZ signaling pathway. Targeting the SPARC-YAP/TAZ axis might provide a new strategy for inhibiting fibrosis formation after trabeculectomy.
EXPERIMENTAL CELL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Kavon Karrobi, Anup Tank, Mohammad Ahsan Fuzail, Madhumathi Kalidoss, Karissa Tilbury, Muhammad Zaman, Jacopo Ferruzzi, Darren Roblyer
Summary: Cancer cells are sensitive to the physical properties of their microenvironment, which affect their downstream signaling and metabolic pathways. Using FLIM, researchers studied the metabolic changes in 3D breast spheroids embedded in collagen with different densities. The results showed that cells in contact with the extracellular matrix and those that migrated further exhibited metabolic shifts towards oxidative phosphorylation (OXPHOS).
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Yushi Yoshimasa, Tomoka Takao, Satomi Katakura, Shoko Tomisato, Hirotaka Masuda, Mamoru Tanaka, Tetsuo Maruyama
Summary: The use of ECM-based scaffolds, such as the decellularized endometrial scaffold (DES), can enhance the regeneration of endometrial stroma in the uterus. However, additional intervention(s) are needed to induce the regeneration of luminal and glandular epithelia. The prevention of adhesions alone can also lead to endometrial stroma regeneration, but to a lesser degree compared to DES.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Elizabeth I. Harper, Ashani T. Weeraratna
Summary: Cancer is an age-related disease, and the changes in tumor microenvironment caused by aging of extracellular matrix and immune system need to be better understood. Multidisciplinary studies can provide new insights for the development of new therapeutics.
Article
Biochemistry & Molecular Biology
Ao Chen, Sha Liao, Mengnan Cheng, Kailong Ma, Liang Wu, Yiwei Lai, Xiaojie Qiu, Jin Yang, Jiangshan Xu, Shijie Hao, Xin Wang, Huifang Lu, Xi Chen, Xing Liu, Xin Huang, Zhao Li, Yan Hong, Yujia Jiang, Jian Peng, Shuai Liu, Mengzhe Shen, Chuanyu Liu, Quanshui Li, Yue Yuan, Xiaoyu Wei, Huiwen Zheng, Weimin Feng, Zhifeng Wang, Yang Liu, Zhaohui Wang, Yunzhi Yang, Haitao Xiang, Lei Han, Baoming Qin, Pengcheng Guo, Guangyao Lai, Pura Munoz-Canoves, Patrick H. Maxwell, Jean Paul Thiery, Qing-Feng Wu, Fuxiang Zhao, Bichao Chen, Mei Li, Xi Dai, Shuai Wang, Haoyan Kuang, Junhou Hui, Liqun Wang, Ji-Feng Fei, Ou Wang, Xiaofeng Wei, Haorong Lu, Bo Wang, Shiping Liu, Ying Gu, Ming Ni, Wenwei Zhang, Feng Mu, Ye Yin, Huanming Yang, Michael Lisby, Richard J. Cornall, Jan Mulder, Mathias Uhlen, Miguel A. Esteban, Yuxiang Li, Longqi Liu, Xun Xu, Jian Wang
Summary: Spatially resolved transcriptomic technologies enable us to study complex biological processes such as mammalian embryogenesis. However, current methods have limitations in resolution, gene capture, and field of view, which hinders their systematic application to large and three-dimensional mid- and late-gestation embryos. In this study, we developed Stereo-seq, a spatially enhanced resolution omics-sequencing method, by combining DNA nanoball-patterned arrays and in situ RNA capture. We used Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas, MOSTA, which provides single cell resolution and high sensitivity for mapping the kinetics and directionality of transcriptional variation during mouse organogenesis. By utilizing this atlas, we investigated the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues like the dorsal midbrain. Our panoramic atlas will facilitate in-depth research into long-standing questions about normal and abnormal mammalian development.
Article
Multidisciplinary Sciences
Lei Han, Xiaoyu Wei, Chuanyu Liu, Giacomo Volpe, Zhenkun Zhuang, Xuanxuan Zou, Zhifeng Wang, Taotao Pan, Yue Yuan, Xiao Zhang, Peng Fan, Pengcheng Guo, Yiwei Lai, Ying Lei, Xingyuan Liu, Feng Yu, Shuncheng Shangguan, Guangyao Lai, Qiuting Deng, Ya Liu, Liang Wu, Quan Shi, Hao Yu, Yunting Huang, Mengnan Cheng, Jiangshan Xu, Yang Liu, Mingyue Wang, Chunqing Wang, Yuanhang Zhang, Duo Xie, Yunzhi Yang, Yeya Yu, Huiwen Zheng, Yanrong Wei, Fubaoqian Huang, Junjie Lei, Waidong Huang, Zhiyong Zhu, Haorong Lu, Bo Wang, Xiaofeng Wei, Fengzhen Chen, Tao Yang, Wensi Du, Jing Chen, Shibo Xu, Juan An, Carl Ward, Zongren Wang, Zhong Pei, Chi-Wai Wong, Xiaolei Liu, Huafeng Zhang, Mingyuan Liu, Baoming Qin, Axel Schambach, Joan Isern, Liqiang Feng, Yan Liu, Xiangyu Guo, Zhen Liu, Qiang Sun, Patrick H. Maxwell, Nick Barker, Pura Munoz-Canoves, Ying Gu, Jan Mulder, Mathias Uhlen, Tao Tan, Shiping Liu, Huanming Yang, Jian Wang, Yong Hou, Xun Xu, Miguel A. Esteban, Longqi Liu
Summary: Studying tissue composition and function in non-human primates is crucial for understanding the nature of human species. This study presents a large-scale cell transcriptomic atlas of the non-human primate Macaca fascicularis, providing a vast annotated resource for studying a species closely related to humans. The atlas has been used to reconstruct cell-cell interaction networks, map the distribution of receptors for viruses causing human infectious diseases, and establish potential clinical associations with human genetic diseases.
Article
Oncology
Esther Schoutrop, Lidia Moyano-Galceran, Stephanie Lheureux, Jonas Mattsson, Kaisa Lehti, Hanna Dahlstrand, Isabelle Magalhaes
Summary: This article summarizes the current knowledge on the development and metastatic progression of ovarian cancer, with a specific focus on the characteristics and functions of the immunosuppressive tumor microenvironment. Additionally, current and future treatment modalities are discussed, and an overview of different experimental models used for developing novel therapies is provided.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Jordi Gonzalez-Molina, Katharina Miria Kirchhof, Bhavik Rathod, Lidia Moyano-Galceran, Maria Calvo-Noriega, Georgia Kokaraki, Astrid Bjorkoy, Monika Ehnman, Joseph W. Carlson, Kaisa Lehti
Summary: Fibrillar collagens have been found to promote cell proliferation, migration, and survival in various epithelial cancers, but their impact on soft tissue sarcoma behavior is not well understood. However, this study unexpectedly reveals that fibrillar collagen-related gene expression is associated with a favorable prognosis in rhabdomyosarcoma. By using collagen matrices with different stiffness and in vivo-like microarchitectures, the study demonstrates that DDR1 activation induces apoptosis, while integrin beta 1 promotes cell survival in 3D rhabdomyosarcoma cell cultures. Mechanistically, the collagen-induced apoptosis is a result of both DDR1-independent and synergistic DDR1-dependent TRPV4-mediated response to mechanical confinement. These findings suggest that dense microfibrillar collagen-rich microenvironments are detrimental to rhabdomyosarcoma cells through an apoptotic response orchestrated by DDR1 signaling and mechanical confinement, which may explain the preference of rhabdomyosarcoma cells to grow in and metastasize to low fibrillar collagen microenvironments such as the lung.
Article
Dermatology
Olga Bugaeva, Pilvi Maliniemi, Wenche S. Prestvik, Eeva Leivo, Nicolas Kluger, Alexander Salava, Sanna Virtanen, Kirsi Jantti, Olli Saksela, Kaisa Lehti, Paula Kujala, Kai Krohn, Annamari Ranki
Summary: This study examined the expression of NAV3 in relation to MMP14 in different melanoma samples. The results showed that NAV3 copy number changes were found in a majority of primary melanomas, with deletions being the most common. NAV3 was also found to be localized at the leading edge of migrating melanoma cells in vitro. Furthermore, the expression of NAV3 correlated with MMP14 in the majority of primary melanomas, but this correlation decreased in thicker tumors. These findings suggest that the lack of both NAV3 and MMP14 may promote melanoma progression.
ACTA DERMATO-VENEREOLOGICA
(2023)
Article
Oncology
Jordi Gonzalez-Molina, Paula Hahn, Raul Maia Falcao, Okan Gultekin, Georgia Kokaraki, Valentina Zanfagnin, Tirzah Braz Petta, Kaisa Lehti, Joseph W. W. Carlson
Summary: This study explored the impact of fibrillar collagens on uterine leiomyosarcoma (uLMS) and found that uLMS tumors have low collagen density and increased expression of collagen-remodeling genes compared to uterine leiomyomas (LM)．The overexpression of matrix metalloproteinase-14 (MMP14) in uLMS was found to support uLMS cell proliferation, and uLMS cells were found to be less sensitive to changes in collagen substrate stiffness. Additionally, enhanced basal yes-associated protein 1 (YAP) activity was observed in uLMS cells, which sustains their growth in low-stiffness substrates. These findings suggest that matrix remodeling and YAP may be potential therapeutic targets for uLMS．
MOLECULAR ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Lara Closset, Okan Gultekin, Sahar Salehi, Dhifaf Sarhan, Kaisa Lehti, Jordi Gonzalez-Molina
Summary: Targeting the tumour immune microenvironment (TIME) by cancer immunotherapy has improved patient outcomes, but response to these treatments varies depending on the cancer type. The extracellular matrix (ECM) plays a major role in immune cell function and resistance to therapies. Both cancer therapies and TIME-ECM crosstalk have implications for tumor progression and clinical intervention. Co-targeting of ECM and TIME with oncological therapies shows promise for improving treatment outcomes.
Meeting Abstract
Medicine, Research & Experimental
Valentina Zanfagnin, Okan Gultekin, Raul Maia Falcao, Kaisa Lehti, Tirzah Braz Petta, Joseph Carlson
LABORATORY INVESTIGATION
(2023)
