Review
Biochemistry & Molecular Biology
Yaru Yang, Jiayan Li, Wangrui Lei, Haiying Wang, Yunfeng Ni, Yanqing Liu, Huanle Yan, Yifan Tian, Zheng Wang, Zhi Yang, Shulin Yang, Yang Yang, Qiang Wang
Summary: Cancer is a complex disease caused by genetic mutations and/or epigenetic changes, and it poses the biggest challenge worldwide. Cytokines, particularly chemokines, play a significant role in various human cancers by affecting homeostasis, immune function, and facilitating cancer development stages such as invasion, metastasis, and angiogenesis. Specifically, chemokines such as CXCL12 and its receptors CXCR4 and CXCR7 exert extensive influence on tumor cell behavior, including proliferation, survival, angiogenesis, metastasis, and tumor microenvironment, making them crucial players in the initiation and progression of cancers such as leukemia, breast cancer, lung cancer, prostate cancer, and multiple myeloma. This review aims to summarize the recent research progress and future challenges related to the CXCL12-CXCR4/CXCR7 signaling axis in cancer, emphasizing the potential of utilizing CXCL12-CXCR4/CXCR7 as a biomarker or therapeutic target for cancer treatment and providing valuable insights for the development of targeted cancer therapies.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Mahdieh Mehrpouri
Summary: CXCL12/CXCR4 and CXCL12/CXCR7 axes play a key role in hematopoiesis and their aberrant expression may lead to the development of leukemia. Various therapeutic interventions have been developed to target these axes in leukemic cells, showing promising results in pre-clinical and clinical studies.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Oncology
Masakazu Goto, Yukiko Shibahara, Cristina Baciu, Frances Allison, Jonathan C. Yeung, Gail E. Darling, Mingyao Liu
Summary: This study found that high expression of CXCR7 is associated with poor prognosis in patients with esophageal adenocarcinoma, and the combination of high expression of CXCR7 and CXCL12 has a stronger association with prognosis. Additionally, high expression of both CXCR7 and CXCL12 was identified as an independent prognostic factor for overall and disease-free survival in patients with esophageal adenocarcinoma. Further research with larger sample sizes is warranted to explore the potential of this biomarker.
ANNALS OF SURGICAL ONCOLOGY
(2021)
Article
Oncology
Crescenzo D'Alterio, Anna Spina, Laura Arenare, Paolo Chiodini, Maria Napolitano, Francesca Galdiero, Luigi Portella, Vittorio Simeon, Simona Signoriello, Francesco Raspagliesi, Domenica Lorusso, Carmela Pisano, Nicoletta Colombo, Gian Franco Zannoni, Nunzia Simona Losito, Rossella De Cecio, Giosue Scognamiglio, Daniela Califano, Daniela Russo, Valentina Tuninetti, Maria Carmela Piccirillo, Piera Gargiulo, Francesco Perrone, Sandro Pignata, Stefania Scala
Summary: Despite advances in research on epithelial ovarian cancer, this study systematically evaluated the CXCR4-CXCL12-CXCR7 axis in tumor and stromal cells, identifying a potential prognostic and therapeutic target in high CXCL12 expression in cancer cells. The study highlights the importance of further investigating the CXCL12 axis to improve treatment efficacy in EOC patients.
Article
Cell Biology
Crescenzo D'Alterio, Alessandro Giardino, Giosue Scognamiglio, Giovanni Butturini, Luigi Portella, Giuseppe Guardascione, Isabella Frigerio, Marco Montella, Stefano Gobbo, Guido Martignoni, Vincenzo Napolitano, Ferdinando De Vita, Fabiana Tatangelo, Renato Franco, Stefania Scala
Summary: CXCR4-CXCL12 evaluation in PDAC identifies prognostic categories and could guide therapeutic approaches.
Article
Biochemistry & Molecular Biology
Thaynan Lopes Goncalves, Luanna Prudencio de Araujo, Valeria Pereira Ferrer
Summary: The chemokine stromal cell-derived-factor 1 (SDF)-1/CXCL12 acts through its receptors CXCR4 and CXCR7, leading to cell survival, proliferation, and migration in breast cancer and glioblastoma. Tamoxifen (TMX), a selective estrogen receptor modulator, has shown potential antitumor activity against these tumors by inhibiting estrogen-regulated genes and targeting various proteins. This review discusses the role of the CXCL12-CXCR4-CXCR7 chemokine axis in tumor biology and suggests TMX as a potential modulator in breast cancer and a possible target in glioblastoma. Further studies on TMX's effect on the CXCL12-CXCR4-CXCR7 axis in glioblastoma could benefit patients, as this axis is associated with therapy resistance.
Article
Immunology
Paola Antonello, Diego U. Pizzagalli, Mathilde Foglierini, Serena Melgrati, Egle Radice, Sylvia Thelen, Marcus Thelen
Summary: Chemotaxis is an essential process in tumors metastasis, and in this study, ACKR3 was found to control the migration of lymphoma cells in response to CXCL12. The interaction between LTB4 and CXCL12 enhances the migration of lymphoma cells, providing a novel mechanism for cell-to-cell-induced migration.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Tripti Khare, Marc Bissonnette, Sharad Khare
Summary: Chemokines like CXCL12 play a significant role in cancer growth and metastasis, with receptors like CXCR4 and CXCR7 being potential targets for treatment strategies in colorectal cancer. Targeting the CXCL12-CXCR4/CXCR7 axis shows promise in developing new therapies for CRC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Peng Liu, Hongke Sun, Xin Zhou, Qiaozhu Wang, Feng Gao, Yuping Fu, Tong Li, Yixin Wang, Yingqi Li, Boyuan Fan, Xiaoli Li, Tiannan Jiang, Xinghua Qin, Qiangsun Zheng
Summary: This study identified three hub genes involved in atrial fibrillation (AF), with the CXCL12/CXCR4 axis standing out as a potent target for AF prevention. In vivo investigation showed that inhibiting CXCR4 reduced AF inducibility and duration by decreasing atrial inflammation and structural remodeling. Mechanistically, this effect was achieved by reducing immune cell recruitment and suppressing signaling pathways in the atria. These findings suggest that CXCL12/CXCR4 axis may be a potential therapeutic target for AF.
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Parishmita Sarma, Carlo Marion C. Carino, Deeksha Seetharama, Shubhi Pandey, Hemlata Dwivedi-Agnihotri, Xue Rui, Yubo Cao, Kouki Kawakami, Poonam Kumari, Yu-Chih Chen, Kathryn E. Luker, Prem N. Yadav, Gary D. Luker, Stephane A. Laporte, Xin Chen, Asuka Inoue, Arun K. Shukla
Summary: Chemokine receptors are G protein-coupled receptors (GPCRs) involved in immune responses and characterized by ligand promiscuity. Here, the authors characterize signaling through chemokine receptors CXCR4 and CXCR7, with insights into intrinsic-bias encoded in the CXCR4-CXCR7 system.
NATURE COMMUNICATIONS
(2023)
Review
Oncology
Aissata Aimee Goita, Dominique Guenot
Summary: This review discusses the role of the CXCL12 axis and its receptors CXCR4 and CXCR7 in colorectal cancer, highlighting their potential as therapeutic targets.
Article
Cell Biology
Liam A. Ridge, Dania Kewbank, Dagmar Schuetz, Ralf Stumm, Peter J. Scambler, Sarah Ivins
Summary: The study shows that CXCL12 signaling through its receptor CXCR4 plays distinct roles in different stages of SLV development, guiding cellular distribution and regulating cell proliferation. The atypical chemokine receptor CXCR7 may have a role in regulating ligand bioavailability during SLV morphogenesis.
Article
Microbiology
Kathryn Wright, Kumudika de Silva, Karren M. Plain, Auriol C. Purdie, Tamika A. Blair, Lain G. Duggin, Warwick J. Britton, Stefan H. Oehlers
Summary: Mycobacterial infections cause significant disease burden and pathogenic mycobacteria induce host miR-206 expression to suppress protective neutrophil recruitment, promoting permissive granuloma microenvironments in the host.
Article
Oncology
Christian Koch, Nina Charlotte Fischer, Malte Puchert, Juergen Engele
Summary: This study investigates the combined effects of CXCL12 and CXCL11 on specific tumor cells and reveals that their impact on cell migration, invasion, proliferation, and apoptosis depends on cell type and function. The findings suggest the potential limitations of targeting CXCR3, CXCR4, or CXCR7 selectively in cancer patients and highlight the importance of individualized targeting strategies.
Review
Oncology
Juan Carlos Lopez-Gil, Laura Martin-Hijano, Patrick C. Hermann, Bruno Sainz Jr
Summary: This review summarizes the role of CXCL12 and its receptors in cancer stem cells and their niche, discusses therapeutic options, and highlights the need for a comprehensive review on the topic.
Review
Physiology
Kerstin Hartmann, Mascha Koenen, Sebastian Schauer, Stephanie Wittig-Blaich, Mubashir Ahmad, Ulrike Baschant, Jan P. Tuckermann
PHYSIOLOGICAL REVIEWS
(2016)
Article
Multidisciplinary Sciences
Mubashir Ahmad, Torsten Kroll, Jeanette Jakob, Alexander Rauch, Aspasia Ploubidou, Jan Tuckermann
SCIENTIFIC REPORTS
(2018)
Review
Immunology
Mubashir Ahmad, Yasmine Hachemi, Kevin Paxian, Florian Mengele, Mascha Koenen, Jan Tuckermann
FRONTIERS IN IMMUNOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Zeynab Najafova, Peng Liu, Florian Wegwitz, Mubashir Ahmad, Liezel Tamon, Robyn Laura Kosinsky, Wanhua Xie, Steven A. Johnsen, Jan Tuckermann
Summary: The role of RNF40-mediated H2B monoubiquitination in bone formation and remodeling is crucial, as shown by the study. Loss of RNF40 affects osteoblast differentiation stage-dependently and results in impaired bone formation but increased bone mass due to disrupted bone cell crosstalk. The mechanism involves modulation of RANKL expression in osteoblasts, impacting osteoclast number and function.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Endocrinology & Metabolism
Sooyeon Lee, Peng Liu, Mubashir Ahmad, Jan P. Tuckermann
Summary: The study reveals that treatment with LIF can rescue the decreased early osteogenic differentiation and mineralization of osteoblasts induced by GCs, and in vivo LIF treatment protects against GC-mediated trabecular bone loss. This protection is attributed to LIF rescuing the decreased activity of Stat3, MAPK, and Akt signaling pathways caused by GCs, suggesting a potential new therapeutic strategy to prevent GC-induced bone loss.
Article
Biochemistry & Molecular Biology
Benjamin Thilo Krueger, Lena Steppe, Sabine Vettorazzi, Melanie Haffner-Luntzer, Sooyeon Lee, Ann-Kristin Dorn, Anita Ignatius, Jan Tuckermann, Mubashir Ahmad
Summary: Long-term use of glucocorticoids can lead to glucocorticoid-induced osteoporosis, and current drugs for treating bone loss are expensive or have major side effects. Therefore, finding cost-effective small-molecule inhibitors is necessary. This study found that inhibition of Cdk5 improves glucocorticoid-induced bone loss, but does not reverse compromised fracture healing.
Article
Endocrinology & Metabolism
Mubashir Ahmad, Nadine Stirmlinger, Irfana Jan, Ulrich Stifel, Sooyeon Lee, Marcel Weingandt, Ulrike Kelp, Juergen Bockmann, Anita Ignatius, Tobias M. Boeckers, Jan Tuckermann
Summary: Mutations in the postsynaptic scaffold protein Shank2 are associated with autism spectrum disorders (ASD) and an increased risk of fractures in affected patients. This study investigates the direct role of Shank2 in regulating bone mass. The findings indicate that Shank2 is expressed in bone and plays a crucial role in osteoblast differentiation and bone formation. The interaction between Shank2 and proteins known from the central nervous system is identified as important for osteoblast differentiation.
Article
Endocrinology & Metabolism
Melanie Haffner-Luntzer, Deniz Ragipoglu, Mubashir Ahmad, Astrid Schoppa, Lena Steppe, Verena Fischer, Julia Luther, Timur Yorgan, Ernesto Bockamp, Michael Amling, Thorsten Schinke, Anita Ignatius
Summary: Despite improvements in fracture care, a percentage of fractures still heal poorly. The study investigated the potential of Wnt1 as a molecule to improve bone fracture healing. The results showed that Wnt1 promotes bone formation during fracture healing through YAP/BMP signaling. This suggests that Wnt1 could be used as a therapeutic agent for orthopedic complications.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Review
Endocrinology & Metabolism
Merle Stein, Florent Elefteriou, Bjorn Busse, Imke A. K. Fiedler, Ronald Young Kwon, Eric Farrell, Mubashir Ahmad, Anita Ignatius, Liam Grover, Liesbet Geris, Jan Tuckermann
Summary: Major achievements in bone research have relied on animal models and in vitro systems. However, the ethical debate surrounding animal experimentation and advancements in in vitro and in silico techniques have challenged their use. This review provides an overview of the strengths and limitations of animal models, as well as in vitro and in silico technologies, in skeletal research. The authors propose that a combination of the right animal model and state-of-the-art technology is essential for advancing bone research.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Cell & Tissue Engineering
Mubashir Ahmad, Benjamin Thilo Krueger, Torsten Kroll, Sabine Vettorazzi, Ann-Kristin Dorn, Florian Mengele, Sooyeon Lee, Sayantan Nandi, Dilay Yilmaz, Miriam Stolz, Naveen Kumar Tangudu, David Carro Vazquez, Johanna Pachmayr, Ion Cristian Cirstea, Maja Vujic Spasic, Aspasia Ploubidou, Anita Ignatius, Jan Tuckermann
Summary: This study identified Cdk5 as a suppressor of osteoblast differentiation through unbiased kinome RNAi screening. Cdk5 knockdown or inhibition enhanced osteoblastogenesis in vitro, and it was found to regulate osteoblast differentiation through the MAPK pathway. These findings suggest that Cdk5 may be a potential therapeutic target for treating osteoporosis and improving fracture healing.
Article
Endocrinology & Metabolism
Alessa Wagner, Betuel Alan, Dilay Yilmaz, Mubashir Ahmad, Peng Liu, Naveen Kumar Tangudu, Jan P. Tuckermann, Maja Vujic Spasic
Article
Cell Biology
Jeffrey Maslanka, Gretel Torres, Jennifer Londregan, Naomi Goldman, Daniel Silberman, John Somerville, James E. Riggs
Summary: This study investigates the immunobiology of the peritoneum in ovarian cancer, revealing reduced B1 cells in the ascites and selective loss of B1 and marginal zone B cell subsets in the spleen. These findings suggest a correlation between the depletion of B cell subsets and the influx of myeloid-derived suppressor cells during ovarian cancer.
CELLULAR IMMUNOLOGY
(2024)