Article
Medicine, Research & Experimental
Ilona Berestjuk, Margaux Lecacheur, Alexandrine Carminati, Serena Diazzi, Christopher Rovera, Virginie Prod'homme, Mickael Ohanna, Ana Popovic, Aude Mallavialle, Frederic Larbret, Sabrina Pisano, Stephane Audebert, Thierry Passeron, Cedric Gaggioli, Christophe A. Girard, Marcel Deckert, Sophie Tartare-Deckert
Summary: The study reveals that physical and structural signals from fibroblast-derived ECM can cause the antiproliferative responses to BRAF/MEK inhibitors to fail in melanoma. Drug-induced linear clustering of DDR1 and DDR2 mediates ECM-mediated drug resistance. Targeting DDR1 and DDR2 can overcome resistance to BRAF-targeted therapy mediated by ECM.
EMBO MOLECULAR MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Ahmed Elkamhawy, Qili Lu, Hossam Nada, Jiyu Woo, Guofeng Quan, Kyeong Lee
Summary: DDR is a crucial collagen-activated receptor tyrosine kinase that regulates essential cellular processes, and its dysregulation is associated with various cancers and diseases. Efforts have been made in the development of DDR inhibitors, focusing on the progress of DDR1 and DDR2 inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Dentistry, Oral Surgery & Medicine
Yuhan Wang, Bing Han, Kaining Liu, Xiaoyan Wang
Summary: This study determined the expression of DDR1 in hPDLCs and found that DDR1 plays an important role in the migration and adhesion of hPDLCs. The study also suggests that DDR1 may be regulated via the MEK-ERK1/2 signaling pathway.
JOURNAL OF PERIODONTAL RESEARCH
(2022)
Review
Cell Biology
Rui Ma, Xudong Xie, Lei Zhao, Yafei Wu, Jun Wang
Summary: Periodontitis is a chronic inflammatory disease with high prevalence and economic burden, and discoidin domain receptors (DDRs) play potential roles in the pathogenesis of periodontitis by controlling cell migration, adhesion, and extracellular matrix remodeling in periodontal tissues rich in collagen.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jiali Xie, Dan Meng, Yihao Li, Ruoyu Li, Ping Deng
Summary: A docking assessment of the DDR1 crystal structures was conducted to find potential inhibitors with target specificity. Several promising compounds were identified and validated through molecular dynamics simulations, indicating their potential as DDR1 inhibitors.
MOLECULAR DIVERSITY
(2023)
Article
Biochemistry & Molecular Biology
Quinn A. Bonafiglia, Yu-Qing Zhou, Guangpei Hou, Rhidita Saha, Ying-Han R. Hsu, Jonah Burke-Kleinman, Michelle P. Bendeck
Summary: Pulmonary hypertension is a disease characterized by elevated pulmonary arterial pressure, leading to right ventricular dysfunction and failure. This study shows that the DDR1 gene deletion results in abnormal muscularization of pulmonary arteries and impaired alveolar development, causing pulmonary hypertension and bronchopulmonary dysplasia.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Review
Oncology
Hang Gong, Hui-Mei Xu, De-Kui Zhang
Summary: DDRs are receptor tyrosine kinases that bind to extracellular collagens and are rarely expressed in normal liver tissues. Recent studies have shown that DDRs play a significant role in premalignant and malignant liver diseases. DDR1 promotes inflammation, fibrosis, invasion, migration, and liver metastasis of tumor cells, while DDR2 may have different roles in early-stage liver injury, chronic liver fibrosis, and metastatic liver cancer. This review provides a detailed description of these findings and aims to provide new insights for cancer treatment and translation from bench to bedside.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Shuai Wang, Yanping Xie, Aina Bao, Jing Li, Tingting Ye, Chu Yang, Shufang Yu
Summary: Nilotinib, a potent DDR1 inhibitor, demonstrated potential antitumor activity in the treatment of breast cancer by inducing apoptosis and blocking cell migration. Targeting DDR1 could potentially impact survival and metabolism in breast cancer, with nilotinib showing promise as a candidate for breast cancer treatment.
Article
Biochemistry & Molecular Biology
Andres Martin Toscani, Pablo Aguilera, Federico Coluccio Leskow
Summary: The physical interaction between ErbB2 and DDR1 receptors in breast cancer cells suggests their involvement in the signaling pathway. These receptors are coexpressed in normal mammary gland but not in breast tumors.
Article
Oncology
Chenlu Wu, Jiafei Ying, Mei Dai, Jing Peng, Danhua Zhang
Summary: The study found that DDR2 and IFITM1 are highly expressed in breast cancer and are associated with poor clinical outcomes and patient survival. Knockdown of DDR2 or IFITM1 can inhibit the viability and invasiveness of breast cancer cells and restrict tumor growth. Simultaneous knockdown of IFITM1 and DDR2 can more effectively suppress breast cancer development.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Article
Oncology
Zhigang Zhao, Shankun Zhao, Lianmin Luo, Qian Xiang, Zhiguo Zhu, Jiamin Wang, Yangzhou Liu, Jintai Luo
Summary: The study demonstrates a tumor-suppressive role of miR-199b-5p in invasion and metastasis of PCa by inhibiting DDR1 expression and EMT, leading to poor prognosis in patients. Additionally, the miR-199b-5p-DDR1-ERK signaling axis represents a novel mechanism for regulating EMT in PCa metastases.
BRITISH JOURNAL OF CANCER
(2021)
Review
Oncology
Sandra Majo, Patrick Auguste
Summary: This study explores the role of collagens in the tumor microenvironment, as well as the different functions of DDRs in various cancers. It also discusses the complexity of anti-DDR therapies in cancer treatment, as well as the key factors in tumor development and metastasis.
Article
Biochemistry & Molecular Biology
Chen-Wei Chiang, Yun-Shih Lin, Fu-Ling Chang, Tsai-Yu Lin, Keng-Chang Tsai, Wei-Chun HuangFu, Yu-Ching Lee
Summary: Studies have shown that high expression of EphA4 in gastric cancer tissues is associated with unfavorable clinical pathological characteristics. In this study, the generated scFv S3 was found to bind to endogenous EphA4 in gastric cancer cells, inhibiting the growth and migration of cancer cells. The administration of scFv S3 also resulted in decreased signaling molecules and improved therapeutic effects in a xenograft model. Furthermore, scFv S3 was able to degrade EphA4 molecules in tumor tissues and generate essential ionic bonding with the target protein.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Hsin-Chiao Chou, Sung-Yen Lin, Liang-Yin Chou, Mei-Ling Ho, Shu-Chun Chuang, Tsung-Lin Cheng, Lin Kang, Yi-Shan Lin, Yan-Hsiung Wang, Chun-Wang Wei, Chung-Hwan Chen, Chau-Zen Wang
Summary: The study reveals that DDR1 plays a crucial role in adult bone development by regulating osteoblast and osteocyte functions, and DDR1 knockout results in bone loss, suggesting DDR1 as a potential therapeutic target for managing cancellous bone loss.
Article
Biochemistry & Molecular Biology
Yi-xiao Xiong, Xiao-chao Zhang, Jing-han Zhu, Yu-xin Zhang, Yong-long Pan, Yu Wu, Jian-ping Zhao, Jun-jie Liu, Yuan-xiang Lu, Hui-fang Liang, Zhan-guo Zhang, Wan-guang Zhang
Summary: Cancer stem cells (CSCs) are a minority population of cancer cells with stemness and multiple differentiation potentials, leading to cancer progression and therapeutic resistance. However, the concrete mechanism of CSCs in hepatocellular carcinoma (HCC) remains obscure. We found that in advanced HCC tissues, collagen I was upregulated, which is consistent with the expression of its receptor DDR1. Collagen I-induced DDR1 activation enhanced HCC cell stemness in vitro and in vivo. The combined inhibition of DDR1 and YAP synergistically abrogated HCC cell stemness in vitro and tumorigenesis in vivo. A radiomic model based on T2 weighted images can noninvasively predict collagen I expression. These findings reveal the molecular basis of collagen I-DDR1 signaling inhibiting Hippo signaling and highlight the role of CD44/DDR1/YAP axis in promoting cancer cell stemness, suggesting that DDR1 and YAP may serve as novel prognostic biomarkers and therapeutic targets in HCC.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Cell Biology
Patrick Auguste, Birgit Leitinger, Christelle Liard, Virginie Rocher, Laurent Azema, Frederic Saltel, David Santamaria
JOURNAL OF CELL SCIENCE
(2020)
Article
Oncology
Sandra Majo, Sarah Courtois, Wilfried Souleyreau, Andreas Bikfalvi, Patrick Auguste
FRONTIERS IN ONCOLOGY
(2020)
Editorial Material
Oncology
Veronique Trezeguet, Sarah Lesjean, Philippe Veschambre, Patrick Auguste, Beatrice Turcq, Stephane Ducassou, Aksam Merched, Christophe F. Grosset
BULLETIN DU CANCER
(2020)
Article
Biology
Maeva Dufies, Annelies Verbiest, Lindsay S. Cooley, Papa Diogop Ndiaye, Xingkang He, Nicolas Nottet, Wilfried Souleyreau, Anais Hagege, Stephanie Torrino, Julien Parola, Sandy Giuliano, Delphine Borchiellini, Renaud Schiappa, Baharia Mograbi, Jessica Zucman-Rossi, Karim Bensalah, Alain Ravaud, Patrick Auberger, Andreas Bikfalvi, Emmanuel Chamorey, Nathalie Rioux-Leclercq, Nathalie M. Mazure, Benoit Beuselinck, Yihai Cao, Jean Christophe Bernhard, Damien Ambrosetti, Gilles Pages
Summary: Dufies et al. found high Plk1 expression levels in aggressive clear cell renal cell carcinoma and discovered that Plk1 is transcriptionally upregulated in a manner dependent on HIF-2. They also found that high Plk1 expression is correlated to a poor prognosis and resistance to tyrosine kinase inhibitor against VEGF receptor, suggesting a critical role for hypoxia/HIF-2-induced Plk1 in disease progression.
COMMUNICATIONS BIOLOGY
(2021)
Article
Gastroenterology & Hepatology
Cyril Dourthe, Celine Julien, Sylvaine Di Tommaso, Jean-William Dupuy, Nathalie Dugot-Senant, Alexandre Brochard, Brigitte Le Bail, Jean-Frederic Blanc, Laurence Chiche, Charles Balabaud, Paulette Bioulac-Sage, Frederic Saltel, Anne-Aurelie Raymond
Summary: The study investigates the proteomic profiles of HCA to classify, diagnose and assess prognosis of tumors, providing valuable insights for complex cases where traditional methods may have limitations. The identification of proteomic profiles directly evaluating malignant transformation risk regardless of HCA subtype can potentially improve patient management and clinical outcomes.
Article
Gastroenterology & Hepatology
Joaquim Javary, Nathalie Allain, Zakaria Ezzoukhry, Sylvaine Di Tommaso, Jean-William Dupuy, Pierre Costet, Nathalie Dugot-Senant, Frederic Saltel, Violaine Moreau, Pierre Dubus, Samira Benhamouche-Trouillet
Summary: Previous studies have shown that Reptin is crucial for hepatocyte proliferation in vivo and liver regeneration, as observed in the Reptin(LKO) mouse model. The impaired liver regeneration in Reptin(LKO) mice post partial hepatectomy is associated with decreased cyclin-A expression and mTORC1 and MAPK signaling. The progressive loss of Reptin invalidation in the model leads to atypical liver regeneration, with hypertrophic and proliferative hepatocytes replacing hypotrophic ones.
LIVER INTERNATIONAL
(2021)
Editorial Material
Medicine, Research & Experimental
Manon Ros, Frederic Bard, Frederic Saltel
M S-MEDECINE SCIENCES
(2021)
Review
Oncology
Sandra Majo, Patrick Auguste
Summary: This study explores the role of collagens in the tumor microenvironment, as well as the different functions of DDRs in various cancers. It also discusses the complexity of anti-DDR therapies in cancer treatment, as well as the key factors in tumor development and metastasis.
Article
Biochemistry & Molecular Biology
Lindsay S. Cooley, Justine Rudewicz, Wilfried Souleyreau, Andrea Emanuelli, Arturo Alvarez-Arenas, Kim Clarke, Francesco Falciani, Maeva Dufies, Diether Lambrechts, Elodie Modave, Domitille Chalopin-Fillot, Raphael Pineau, Damien Ambrosetti, Jean-Christophe Bernhard, Alain Ravaud, Sylvie Negrier, Jean-Marc Ferrero, Gilles Pages, Sebastien Benzekry, Macha Nikolski, Andreas Bikfalvi
Summary: By serially passaging mouse renal cancer cells in vivo, researchers generated multiple cell lines with varying aggressiveness and identified distinct molecular markers and gene processes associated with different stages of tumor progression using transcriptome, genome and methylome analyses. Specific biomarkers such as SAA2 and CFB were identified as soluble prognostic and predictive markers of therapeutic response, with machine learning and mathematical modeling highlighting their significant impact on distant metastasis-free survival. A computational model predicting tumor progression and relapse was developed and validated, providing important translational implications for RCC therapy.
Review
Cell Biology
Charles Saby, Erik Maquoi, Frederic Saltel, Hamid Morjani
Summary: This study discusses two important factors that regulate the collagen/DDR1 axis: the level of DDR1 expression and type I collagen remodeling. DDR1 is highly expressed in epithelial-like breast carcinoma cells, while its expression is relatively low in basal-like breast carcinoma cells. Additionally, DDR1 activation depends on the fibrillar organization of type I collagen.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Margaux Sala, Nathalie Allain, Melanie Moreau, Arnaud Jabouille, Elodie Henriet, Aya Abou-Hammoud, Arnaud Uguen, Sylvaine Di-Tommaso, Cyril Dourthe, Anne-Aurelie Raymond, Jean-William Dupuy, Emilie Gerard, Nathalie Dugot-Senant, Benoit Rousseau, Jean-Phillipe Merlio, Anne Pham-Ledart, Beatrice Vergier, Sophie Tartare-Deckert, Violaine Moreau, Frederic Saltel
Summary: Combined therapy with anti-BRAF plus anti-MEK is the first-line treatment for metastatic melanomas. However, tumor cell resistance is a major issue. This study shows that DDR2 inhibition can reduce AXL expression and stress fiber formation in resistant melanoma cells. Furthermore, DDR2 inhibition can control cell and tumor proliferation through the MAP kinase pathway.
Article
Biochemistry & Molecular Biology
Bertrand Chauveau, Anne-Aurelie Raymond, Sylvaine Di Tommaso, Jonathan Visentin, Agathe Vermorel, Nathalie Dugot-Senant, Cyril Dourthe, Jean-William Dupuy, Julie Dechanet-Merville, Jean-Paul Duong Van Huyen, Marion Rabant, Lionel Couzi, Frederic Saltel, Pierre Merville
Summary: This study used proteomics to investigate the glomerular proteome modification in antibody-mediated rejection (ABMR) in kidney transplantation. It identified several proteins related to cellular stress, leukocyte activation, and tissue remodeling that were deregulated in ABMR. These findings may have implications for the diagnosis and treatment of ABMR.
Article
Biochemical Research Methods
Arturo Alvarez-Arenas, Wilfried Souleyreau, Andrea Emanuelli, Lindsay S. Cooley, Jean-Christophe Bernhard, Andreas Bikfalvi, Sebastien Benzekry
Summary: This article presents a method to extract more information from distant metastasis-free survival (DMFS) curves using a mathematical model. The model depends on parameters that quantify tumor growth and metastatic dissemination, and the parameters are determined using least-squares minimization. The study found that including the percentage of patients with metastasis at diagnosis was critical to the robust estimation of the parameters. The impact and identifiability of covariates and their coefficients in the model were also studied.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Gastroenterology & Hepatology
Esra Karatas, Anne-Aurelie Raymond, Celine Leon, Jean-William Dupuy, Sylvaine Di-Tommaso, Nathalie Senant, Sophie Collardeau-Frachon, Mathias Ruiz, Alain Lachaux, Frederic Saltel, Marion Bouchecareilh
Summary: The study showed that PDIA4, a member of the PDI family, plays a crucial role in AATD-mediated liver disease. Silencing PDIA4 or altering its activity through cysteamine treatment can promote Z-AAT secretion and reduce Z aggregates. Therefore, PDI inhibition represents a potential therapeutic approach for treating AATD-mediated liver disease.
Article
Gastroenterology & Hepatology
Margaux Sala, Delphine Gonzales, Thierry Leste-Lasserre, Nathalie Dugot-Senant, Valerie Paradis, Sylvaine Di Tommaso, Jean-William Dupuy, Vincent Pitard, Cyril Dourthe, Amedeo Sciarra, Christine Sempoux, Linda D. Ferrell, Andrew D. Clouston, Gregory Miller, Mathew M. Yeh, Swan Thung, Annette S. H. Gouw, Alberto Quaglia, Jing Han, Ji Huan, Cathy Fan, James Crawford, Yasuni Nakanuma, Kenichi Harada, Brigitte le Bail, Claire Castain, Nora Frulio, Herve Trillaud, Laurent Possenti, Jean-Frederic Blanc, Laurence Chiche, Christophe Laurent, Charles Balabaud, Paulette Bioulac-Sage, Anne Aurelie Raymond, Frederic Saltel
HEPATOLOGY COMMUNICATIONS
(2020)