Article
Cell Biology
Zheyu Zhang, Zezhong Mou, Chenyang Xu, Siqi Wu, Xiyu Dai, Xinan Chen, Yuxi Ou, Yiling Chen, Chen Yang, Haowen Jiang
Summary: circRNA hsa_circ_0007813 is upregulated in bladder cancer and associated with aggressive tumor characteristics and poor prognosis. Knockdown of hsa_circ_0007813 inhibits proliferation, migration, and invasiveness of bladder cancer cells by regulating IGF2R expression via hsa-miR-361-3p sponging, revealing a potential therapeutic target for bladder cancer.
CELL DEATH & DISEASE
(2021)
Review
Oncology
Rik Derynck, Shannon J. Turley, Rosemary J. Akhurst
Summary: TGF beta signaling plays a key role in cancer progression by promoting cancer cell invasion, dissemination, stem cell properties, therapeutic resistance, and the generation of an immunosuppressive environment. Inhibiting TGF beta signaling is considered a crucial avenue to enhance the efficacy of cancer immunotherapies. Understanding and targeting TGF beta signaling mechanisms in tumors and their microenvironment may provide valuable insights for cancer treatment.
NATURE REVIEWS CLINICAL ONCOLOGY
(2021)
Article
Cell Biology
Anqi Wang, Wen Yang, Yue Li, Yang Zhang, Jieqi Zhou, Ruochen Zhang, Weijie Zhang, Jianjie Zhu, Yuanyuan Zeng, Zeyi Liu, Jian-an Huang
Summary: This study reveals that CPNE1 promotes tumorigenesis in NSCLC by interacting with RACK1 and activating the MET signaling pathway. The combination of a MET inhibitor with an EGFR-TKI is more effective in inhibiting tumor growth.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Oncology
Sunil Singh, Astha Lamichhane, Pouria Rafsanjani Nejad, Jacob Heiss, Hannah Baumann, Ravindra Gudneppanavar, Nic D. Leipzig, Michael Konopka, Gary D. Luker, Hossein Tavana
Summary: Using a three-dimensional organotypic tumor model, we investigated the interactions between patient-derived cancer-associated fibroblasts (CAF) and triple-negative breast cancer (TNBC) cells, identifying the predominant secretion of hepatocyte growth factor (HGF) by CAF and its activation of MET receptor tyrosine kinase in TNBC cells. This interaction promoted invasiveness and oncogenic pathway activities in TNBC cells. We also demonstrated resistance to monotherapy in TNBC cells and identified effective drug combinations to inhibit TNBC cell functions. Additionally, we found that HGF from lung fibroblasts enhanced colony formation by TNBC cells, suggesting a potential target for both primary tumorigenesis and lung metastasis in TNBC.
MOLECULAR CANCER RESEARCH
(2022)
Review
Oncology
Yanfei Feng, Zitong Yang, Xin Xu
Summary: c-Met, overexpressed in bladder cancer, is closely associated with noncoding RNA. Studies have shown that c-Met plays a significant role in the development and prognosis of BCa. Therefore, c-Met is considered a potential target for BCa treatment.
CANCER MANAGEMENT AND RESEARCH
(2022)
Review
Oncology
Wei Meng, Tao Chen
Summary: Hepatocellular carcinoma (HCC) is a highly aggressive and lethal malignancy with a rising incidence, requiring novel treatment strategies.
Article
Oncology
Harald Krenzlin, Mykola Zdioruk, Michal O. Nowicki, Tomer Finkelberg, Naureen Keric, Niels Lemmermann, Magdalena Skubal, E. Antonio Chiocca, Charles H. Cook, Sean E. Lawler
Summary: The study suggests that the CMV-induced upregulation of c-MET may be a potential mechanism involved in the effects of CMV on GBM growth.
Article
Biochemistry & Molecular Biology
Julia N. Cheng, Jennifer B. Frye, Susan A. Whitman, Andrew G. Kunihiro, Ritu Pandey, Janet L. Funk
Summary: The study found that tumoral Smad-mediated TGF beta signaling plays a role in driving osteolytic bone metastases in estrogen receptor-positive (ER+) breast cancer. Additionally, the combination of TGF beta and estrogen induced PTHrP expression, leading to bone resorption, and treatment with a pan-TGF beta neutralizing antibody decreased osteolytic ER+ bone metastases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Wenjing Zhang, Xuelian Zhang, Peng Cheng, Kelin Yue, Ming Tang, Yan Li, Qiang Guo, Yu Zhang
Summary: In this study, the researchers investigated the role of HSF4 in colorectal cancer (CRC) progression. They found that HSF4 was significantly upregulated in CRCs compared with normal colonic tissues and was associated with poor outcomes in CRC patients. Functional assays demonstrated that HSF4 promoted cell growth, colony formation, invasion, and tumor growth. Mechanistically, HSF4 was shown to directly bind to the MET promoter and enhance expression of c-MET, thereby activating the ERK1/2 and AKT signaling pathways. Restoration of c-MET expression rescued the inhibitory effects of downregulated HSF4 expression.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Oncology
Megan M. Harper, Miranda Lin, Shadi A. Qasem, Reema A. Patel, Michael J. Cavnar, Prakash K. Pandalai, Mei Gao, Joseph Kim
Summary: This study describes a previously unreported mechanism of PD-1/MET interaction and the oncogenic functionality of PD-1 in pancreatic cancer. The researchers found that PD-1 can induce epithelial-to-mesenchymal transition (EMT) and regulate growth, migration, and invasion in pancreatic cancer cells. Targeting PD-1 and MET together resulted in substantial tumor cell cytotoxicity and growth inhibition. These findings highlight the importance of targeting the PD-1 axis in pancreatic cancer treatment.
Article
Cell Biology
Shouyang Song, Zhen Yu, Yajing You, Chenxi Liu, Xiaoyu Xie, Huanran Lv, Feng Xiao, Qiang Zhu, Chengyong Qin
Summary: This study confirms the crucial role of EGFR/MET in HCC, as they promote liver cancer metastasis by regulating signaling pathways and resisting immune attacks.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Shayin V. Gibson, Elena Tomas Bort, Lucia Rodriguez-Fernandez, Michael D. Allen, Jennifer J. Gomm, Iain Goulding, Ulrich Auf Dem Keller, Andrea Agnoletto, Cathrin Brisken, Barrie Peck, Angus J. Cameron, John F. Marshall, J. Louise Jones, Edward P. Carter, Richard P. Grose
Summary: Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer. However, the overtreatment of DCIS patients is a pressing issue, as evidence suggests that up to half of them would remain with non-threatening disease. In this study, a 3D in vitro model incorporating luminal and myoepithelial cells was used to investigate the role of myoepithelial cells in DCIS progression. The results showed that DCIS-associated myoepithelial cells promote invasion of luminal cells through the collagenase MMP13 and a non-canonical TGF beta - EP300 pathway. This study identifies myoepithelial-derived MMP13 as a potential marker for risk stratification in DCIS patients.
Article
Cell Biology
Xiang Tao, Can Chen, Yingxiang Chen, Luoying Zhang, Jiong Hu, Hongjun Yu, Minglu Liang, Qin Fu, Kai Huang
Summary: This study reveals that beta(2)-adrenergic receptor (beta(2)AR) plays a critical role in liver regeneration by interacting with c-met and activating ERK signaling, leading to increased hepatocyte proliferation.
CELL DEATH & DISEASE
(2022)
Article
Biology
Ines Lahmann, Joscha Griger, Jie-Shin Chen, Yao Zhang, Markus Schuelke, Carmen Birchmeier
Summary: MET and CXCR4 cooperate to protect muscle stem cells against the harsh inflammatory environment encountered in acute muscle injury. Lack of these factors leads to severe apoptosis in early stages of regeneration.
Article
Gastroenterology & Hepatology
Sicheng Fu, Muziying Liu, Chenwen Zhu, Huimin Zhang, Changfeng Zhao, Yaping Xie, Guanghou Chen, Daping Sheng, Jun Pan, Ziqing He, Ying Dai, Yufeng Gao, Xiaomei Li, Lijian Chen, Yeben Qian, Tengchuan Jin, Cheng Sun, Zhigang Tian, Hua Wang, Li Bai
Summary: This study identifies a regulatory subset of MAIT cells (MAITregs) in HCC patients, which have high immunosuppressive potential and contribute to HCC progression. These MAITregs are induced under Treg-inducing conditions and mainly derived from a pre-MAITreg reservoir. The induction and function of MAITregs are promoted by ss 1 adrenergic receptor signaling in pre-MAITregs and MAITregs, respectively.
Article
Gastroenterology & Hepatology
Christian David Schmid, Victor Olsavszky, Manuel Reinhart, Vanessa Weyer, Felix A. Trogisch, Carsten Sticht, Manuel Winkler, Sina W. Kurschner, Johannes Hoffmann, Roxana Ola, Theresa Staniczek, Joerg Heineke, Beate K. Straub, Jens Mittler, Kai Schledzewski, Peter ten Dijke, Karsten Richter, Steven Dooley, Cyrill Geraud, Sergij Goerdt, Philipp-Sebastian Koch
Summary: This study established an HHT mouse model with liver vascular malformations and investigated the role of ALK1 signaling in liver vessel formation and metabolic function. The results showed that hepatic endothelial ALK1 signaling protects from development of vascular malformations and preserves organ-specific endothelial differentiation and angiocrine signaling.
Review
Biotechnology & Applied Microbiology
Milad Ashrafizadeh, Kiavash Hushmandi, Sepideh Mirzaei, Saied Bokaie, Ashkan Bigham, Pooyan Makvandi, Navid Rabiee, Vijay Kumar Thakur, Alan Prem Kumar, Esmaeel Sharifi, Rajender S. Varma, Amir Reza Aref, Marcin Wojnilowicz, Ali Zarrabi, Hassan Karimi-Maleh, Nicolas H. Voelcker, Ebrahim Mostafavi, Gorka Orive
Summary: Green chemistry has shown great promise in biomedical applications, particularly in cancer therapy. Chitosan-based nanoparticles (CS-NPs) serve as a promising carrier for anti-cancer drugs, overcoming drug resistance and enabling synergistic therapy. Various types of nanostructures can be modified with chitosan for efficient delivery of chemotherapeutic agents such as doxorubicin (DOX). The functionalization of CS-NPs with ligands and their pH-sensitive and redox-responsive characteristics further enhance their selectivity and drug release. Considering their high encapsulation efficiency and biocompatibility, significant progress is expected in the clinical translation of CS-NPs.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Hardeep Singh Tuli, Prangya Rath, Abhishek Chauhan, Anuj Ranjan, Seema Ramniwas, Katrin Sak, Diwakar Aggarwal, Manoj Kumar, Kuldeep Dhama, E. Hui Clarissa Lee, Kenneth Chun-Yong Yap, Sharah Mae Capinpin, Alan Prem Kumar
Summary: Cucurbitacins, a group of highly oxidized tetracyclic triterpenoids found in cucumbers, have potential medical uses. They interact with various cellular targets to inhibit cancer cell growth through induction of apoptosis, cell-cycle arrest, anti-metastasis, and anti-angiogenesis. They may also be used in combination with other drugs to overcome treatment resistance in cancer cells. This study focuses on finding molecular targets for cucurbitacins in suppressing malignant processes.
Letter
Oncology
Yang Hao, Sen Ma, Zili Gu, Alireza Haghparast, Timo Schomann, Zhenfeng Yu, Yuanyuan He, Xiaoxv Dong, Luis J. Cruz, Peter ten Dijke
CANCER COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Chuannan Fan, Qian Wang, Thomas B. Kuipers, Davy Cats, Prasanna Vasudevan Iyengar, Sophie C. Hagenaars, Wilma E. Mesker, Peter Devilee, Rob A. E. M. Tollenaar, Hailiang Mei, Peter ten Dijke
Summary: In this study, the researchers found that the long noncoding RNA LITATS1 functions as an epithelial gatekeeper and inhibits epithelial-mesenchymal transition in breast and non-small cell lung cancer cells. They also discovered that LITATS1 enhances the degradation of the TGF-beta type I receptor, leading to the attenuation of TGF-beta/SMAD signaling and EMT.
Article
Medicine, Research & Experimental
Na Young Kim, In Jin Ha, Jae-Young Um, Alan Prem Kumar, Gautam Sethi, Kwang Seok Ahn
Summary: This study found that LGA can effectively inhibit the proliferation, invasive ability, and migration of hepatocellular carcinoma cells, and reduce the occurrence of EMT by suppressing MnSOD expression. This has important implications for the development of novel anti-metastatic agents.
Review
Chemistry, Medicinal
Hui Li Ang, Chakrabhavi Dhananjaya Mohan, Muthu K. Shanmugam, Hin Chong Leong, Pooyan Makvandi, Kanchugarakoppal S. Rangappa, Anupam Bishyaee, Alan Prem Kumar, Gautam Sethi
Summary: Epithelial-mesenchymal transition (EMT) is a crucial process in which epithelial cells transform into mesenchymal cells, playing a significant role in tumor progression and resistance to therapy. Various factors, such as signaling pathways, transcriptional regulators, noncoding RNAs, and epigenetic alterations, are involved in the regulation of EMT. However, despite preclinical data, there is a lack of clinical translation in targeting EMT therapeutically. This review discusses the role of these factors in EMT regulation, the contribution of EMT to drug resistance, and potential therapeutic interventions using natural products and nano-formulations as EMT blockers.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Chuannan Fan, Roman Gonzalez-Prieto, Thomas B. Kuipers, Alfred C. O. Vertegaal, Peter A. van Veelen, Hailiang Mei, Peter ten Dijke
Summary: We identified an unannotated nuclear long noncoding RNA (lncRNA), LETS1, which is not only increased but also perpetuated by TGF-beta signaling. Loss of LETS1 attenuated TGF-beta-induced EMT and migration in breast and lung cancer cells in vitro and extravasation of the cells in a zebrafish xenograft model. LETS1 potentiates TGF-beta-SMAD signaling by stabilizing cell surface T beta RI, thereby forming a positive feedback loop.
Article
Radiology, Nuclear Medicine & Medical Imaging
Lonneke Rotteveel, Alex J. Poot, Esther J. M. Kooijman, Robert C. Schuit, Ingrid Schalij, Xiaoqing Sun, Kondababu Kurakula, Chris Happe, Wissam Beaino, Peter ten Dijke, Adriaan A. Lammertsma, Harm Jan Bogaard, Albert D. Windhorst
Summary: TGFb activity is affected in various diseases, including pulmonary arterial hypertension (PAH). In this study, two ALK5 targeting PET tracers ([C-11]LR111 and [F-18]EW-7197) were assessed for imaging ALK5 in PAH. [C-11]LR111 showed high ALK5 binding in vitro, while [F-18]EW-7197 had the best in vivo results. Therefore, [F-18]EW-7197 is a promising PET tracer for ALK5 imaging in PAH.
Review
Biotechnology & Applied Microbiology
Xin Yuan Lim, Sharah Mae Capinpin, Nagarjun Bolem, Aaron Song Chuan Foo, Wai-Cheong George Yip, Alan Prem Kumar, Daniel Boon Loong Teh
Summary: Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options due to the difficulty of drugs crossing the blood-brain barrier (BBB) and tumor heterogeneity. Nanoparticle (NP) drug carriers have shown promise in targeting cells beyond the BBB. This review focuses on biomimetic NPs in GBM therapy and their potential in overcoming physiological and anatomical challenges.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Maarten van Dinther, Kyle T. Cunningham, Shashi Prakash Singh, Madeleine P. J. White, Tiffany Campion, Claire Ciancia, Peter A. van Veelen, Arnoud H. de Ru, Roman Gonzalez-Prieto, Ananya Mukundan, Chang- Hyeock Byeon, Sophia R. Staggers, Cynthia S. Hinck, Andrew P. Hinck, Peter ten Dijke, Rick M. Maizels
Summary: This study investigates how the murine intestinal helminth, Heligmosomoides polygyrus, evades the host immune system through the release of an immunosuppressive protein called TGM1. The researchers found that TGM1 binds to the cell surface protein CD44, increasing the potency and specificity of TGF-beta signaling in mammalian cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Yuanzhuo Gu, Zhengkui Zhang, Marcel G. M. Camps, Ferry Ossendorp, Ruud H. Wijdeven, Peter ten Dijke
Summary: The genetic circuits allowing cancer cells to evade immune killing through epithelial mesenchymal plasticity are poorly understood. This study found that mesenchymal-like pancreatic cancer cells were more resistant to cytotoxic T lymphocyte (CTL)-mediated killing than epithelial-like cells. Genome-wide CRISPR screens were used to identify the molecular mechanisms underlying this difference. It was discovered that Mes-specific regulators such as Egfr and Mfge8 facilitate immune escape from CD8(+) T cells by inhibiting their proliferation and the production of immune signaling molecules.
Review
Medicine, Research & Experimental
Yang Hao, Zhonghao Ji, Hengzong Zhou, Dongrun Wu, Zili Gu, Dongxu Wang, Peter ten Dijke
Summary: Immune checkpoint inhibitors (ICIs) have shown remarkable success in cancer treatment. However, in cancer patients without sufficient antitumor immunity, blocking the negative signals elicited by immune checkpoints is ineffective. Stimulating immune activation-related pathways and utilizing nanotechnology for targeted delivery show promising potential for enhancing cancer immunotherapy. This review discusses the latest developments in lipid-based nanoparticles (lipid-NPs) for cancer immuno-oncology therapy, focusing on their characteristics, advantages, and potential to enhance STING agonist therapy.
Article
Oncology
Christianne Groeneveldt, Jurriaan Q. Ginkel, Priscilla Kinderman, Marjolein Sluijter, Lisa Griffioen, Camilla Labrie, Diana J. M. van den Wollenberg, Rob C. Hoeben, Sjoerd H. van der Burg, Peter ten Dijke, Lukas J. A. C. Hawinkels, Thorbald van Hall, Nadine van Montfoort
Summary: The absence of T cells in the tumor microenvironment is a barrier to cancer immunotherapy efficacy. Oncolytic viruses, such as reovirus type 3 Dearing (Reo), can recruit CD8(+) T cells to the tumor and enhance immunotherapeutic strategies. However, TGF-beta signaling might hinder the effectiveness of Reo&CD3-bsAb therapy due to its immunoinhibitory characteristics.
CANCER RESEARCH COMMUNICATIONS
(2023)
Review
Immunology
Yuanzhuo Gu, Zhengkui Zhang, Peter ten Dijke
Summary: Immune checkpoint blockade (ICB) therapy is a powerful option for cancer treatment, but many patients are resistant to this treatment. Tumor epithelial-to-mesenchymal plasticity (EMP) plays a critical role in immune escape and ICB resistance in cancer. This review summarizes the role of tumor EMP in ICB resistance and discusses strategies to modulate it for better treatment outcomes.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)