Article
Multidisciplinary Sciences
Sara Garcia-Garcia, Maria Rodrigo-Faus, Noelia Fonseca, Sara Manzano, Balazs Gyorffy, Alberto Ocana, Paloma Bragado, Almudena Porras, Alvaro Gutierrez-Uzquiza
Summary: The study identifies MAP4K4 as a key gene in prostate cancer metastasis, with its deletion or inhibition blocking cell migration and clonogenic properties, suggesting a potential role of MAP4K4 in promoting tumor dissemination and growth. Moreover, the upregulation of HGK correlates with poor prognosis in prostate cancer, indicating its potential use as a prognostic biomarker for predicting aggressive phenotype and metastasis appearance.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Yujiao Zhang, Yizeng Fan, Xin Jing, Lin Zhao, Tianjie Liu, Lu Wang, Lifen Zhang, Shanzhi Gu, Xinhan Zhao, Yan Teng
Summary: Studies have shown that the activation of YAP increases macrophage recruitment, but its role in macrophage polarization, especially in TNBC progression, is still unclear. TNBC cells were found to increase YAP expression in macrophages via OTUD5-mediated deubiquitination and stabilization, leading to polarization towards the M2-like phenotype. Additionally, high expression of YAP in M2-like macrophages was associated with pro-metastatic potential of TNBC cells through the MCP-1/CCR2 pathway, and negatively related to survival. This suggests that targeting YAP(+) M2 macrophages could be a novel therapeutic strategy for TNBC treatment.
Article
Biochemistry & Molecular Biology
Betul Unlu, Begum Kocaturk, Araci M. R. Rondon, Clayton S. Lewis, Nathalie Swier, Rob F. P. van den Akker, Danielle Krijgsman, Iris Noordhoek, Erik J. Blok, Vladimir Y. Bogdanov, Wolfram Ruf, Peter J. K. Kuppen, Henri H. Versteeg
Summary: TF expression in breast cancer is associated with metastasis and cancer stemness, blockade of TF signaling can inhibit metastasis and reduce expression of pro-metastatic markers.
Article
Cell Biology
Luyao Ma, Yeteng Tian, Tao Qian, Wenjun Li, Chengmin Liu, Bizhu Chu, Qian Kong, Renwei Cai, Panzhu Bai, Lisha Ma, Yi Deng, Ruijun Tian, Chuanyue Wu, Ying Sun
Summary: Kindlin-2 is found to be crucial for promoting AR signaling and breast cancer progression. It physically associates with AR and Src, forming a complex that facilitates Src-mediated AR Tyr-534 phosphorylation and signaling, leading to enhanced breast cancer cell proliferation and migration. Depletion of Kindlin-2 suppresses AR signaling, resulting in diminished breast cancer progression.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Joseph W. Saelens, Mollie I. Sweeney, Gopinath Viswanathan, Ana Maria Xet-Mull, Kristen L. Jurcic Smith, Dana M. Sisk, Daniel D. Hu, Rachel M. Cronin, Erika J. Hughes, W. Jared Brewer, Jorn Coers, Matthew M. Champion, Patricia A. Champion, Craig B. Lowe, Clare M. Smith, Sunhee Lee, Jason E. Stout, David M. Tobin
Summary: The human pathogen Mycobacterium tuberculosis can cause lung disease and disseminate to other tissues. This study identified an outbreak of M. tuberculosis with high rates of extrapulmonary dissemination and bone disease. The causal strain carried a full-length ancestral version of the effector protein EsxM, which exacerbated dissemination through enhancement of macrophage motility and egress from granulomas, as well as alterations in macrophage actin dynamics. Reconstitution of ancestral EsxM in a modern attenuated strain altered the migratory mode of infected macrophages and promoted bone disease in a zebrafish model. The presence of a derived nonsense variant in EsxM in major M. tuberculosis lineages suggests a role for EsxM in regulating dissemination.
Review
Developmental Biology
Naoya Yamaguchi, Holger Knaut
Summary: Cell-extracellular matrix interactions are essential for cell anchoring and migration, with focal adhesions (FAs) playing a key role. However, the role of FAs in vivo is still not well understood.
Article
Multidisciplinary Sciences
Lihua Qiang, Yong Zhang, Zehui Lei, Zhe Lu, Shasha Tan, Pupu Ge, Qiyao Chai, Mengyuan Zhao, Xinwen Zhang, Bingxi Li, Yu Pang, Lingqiang Zhang, Cui Hua Liu, Jing Wang
Summary: This research discovers that tuberculosis-causing pathogen Mycobacterium tuberculosis (Mtb) activates iron-dependent cell death, called ferroptosis, through a secreted protein called PtpA, promoting Mtb's pathogenicity and dissemination. The mechanism involves PtpA entering the host cell nucleus and enhancing the methylation of histone H3, inhibiting the expression of glutathione peroxidase 4 (GPX4), ultimately inducing ferroptosis. This study provides insights into the molecular mechanisms of pathogen-induced ferroptosis and suggests a potential tuberculosis treatment by targeting Mtb PtpA-host PRMT6 interface to block GPX4-dependent ferroptosis.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Ming Xiao, Qi Bian, Yimin Lao, Jing Yi, Xueqing Sun, Xuxu Sun, Jie Yang
Summary: Deletion of SUMO-specific protease 3 in macrophages promotes polarization towards the M2 subtype and accelerates breast cancer malignancy. The deficiency of SENP3 leads to increased SUMOylation of Akt1, resulting in hyper-phosphorylation and activation of Akt1, thus facilitating M2 polarization and tumor progression.
MOLECULAR ONCOLOGY
(2022)
Article
Oncology
Kazunori Mori, Masato Higurashi, Fumihiro Ishikawa, Motoko Shibanuma
Summary: This study showed that non-malignant mammary epithelial cells lose reattachment ability before undergoing cell death upon detachment, while breast cancer cells retain integrin levels and efficiently reattach to substrata. The sustained levels of beta 4 integrin, mediated by Rac1, were critical for reattachment ability and lung metastasis of breast cancer cells. High expression of ITGB4 and RAC1 was associated with poor prognosis in patients with breast cancer, suggesting them as potential therapeutic targets to prevent cancer cells from colonizing secondary organs during metastasis.
Article
Oncology
Jie Wang, Jonathan D. Wren, Yingjun Ding, Junxiong Chen, Nikhil Mittal, Chao Xu, Xing Li, Cengxi Zeng, Meng Wang, Jing Shi, Yanhui H. Zhang, Sangyoon J. Han, Xin A. Zhang
Summary: EWI2 acts as a lung cancer suppressor by inhibiting tumor growth and metastasis while enhancing lysosome activity to decrease levels and functions of growth factor receptors and integrins. This study provides a novel therapeutic strategy to overcome resistance to EGFR inhibitors.
Article
Oncology
Derek Dustin, Guowei Gu, Amanda R. Beyer, Sarah K. Herzog, David G. Edwards, Hangqing Lin, Thomas L. Gonzalez, Sandra L. Grimm, Cristian Coarfa, Doug W. Chan, Beom-Jun Kim, O. Jean-Paul De La, Matthew J. Ellis, Dan Liu, Shunqiang Li, Alana L. Welm, Suzanne A. W. Fuqua
Summary: This study identified hyperactivation of RON in ESR1 mutant cells and its association with acquired palbociclib-resistant models. The interaction between RON and IGF-1R was demonstrated, and combination therapy of endocrine therapy with a RON inhibitor effectively decreased organoid growth in ESR1 mutant models. Additionally, the combination therapy also reduced metastasis in an ESR1 Y537S mutant PDX model, suggesting RON/PI3K pathway inhibition as a potential treatment strategy for ESR1 mutant and PalbR MBC patients.
BRITISH JOURNAL OF CANCER
(2021)
Article
Immunology
Qiuhua Yang, Emily Huo, Yongfeng Cai, Zhidan Zhang, Charles Dong, John M. Asara, Huidong Shi, Qingqing Wei
Summary: Excessive renal fibrosis is a common pathology in progressive chronic kidney diseases. In this study, the researchers found that glycolytic pathway genes are upregulated in renal myeloid cells during kidney fibrosis. By inhibiting the glycolytic activator Pfkfb3, they observed reduced fibrosis, decreased macrophage infiltration, and alterations in macrophage subtypes and phenotypes. Mechanistically, they found that glycolytic metabolites stabilize HIF1α, leading to changes in macrophage phenotypes that contribute to renal fibrosis.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Jared L. Casteel, Kasey R. Keever, Christopher L. Ardell, David L. Williams, Detao Gao, Eugene A. Podrez, Tatiana V. Byzova, Valentin P. Yakubenko
Summary: The oxidation of polyunsaturated fatty acids produces carboxyethylpyrrole (CEP), which forms covalent adducts with proteins and affects the inflammatory response. This study found that CEP-modified ECM proteins enhance the adhesion and spreading of M1 macrophages, and CEP modification converts ECM proteins to ligands for the α(D)β(2) integrin, promoting macrophage retention during detrimental inflammation, autoimmunity, and chronic inflammation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Lindsay B. Case, Milagros De Pasquale, Lisa Henry, Michael K. Rosen
Summary: Integrin adhesion complexes (IACs) are cellular compartments where cells sense environmental cues. In vitro research shows that p130Cas and Focal adhesion kinase undergo liquid-liquid phase separation, which promotes integrin clustering and IAC formation.
Article
Oncology
Janet Arras, Keena S. Thomas, Paul J. Myers, Allison M. Cross, Amare D. Osei, Gabriel E. Vazquez, Kristen A. Atkins, Mark R. Conaway, Marieke K. Jones, Matthew J. Lazzara, Amy H. Bouton
Summary: The study found that high expression of BCAR3 in TNBC is associated with reduced patient survival, and BCAR3 is crucial for TNBC tumor growth. BCAR3 is correlated with MET receptor signaling, and both proteins participate in a single pathway controlling proliferation and migration of TNBC cells. The functional interaction of BCAR3-MET appears to differ in TNBC with different genetic backgrounds.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Oncology
N. C. Turner, C. Swift, B. Jenkins, L. Kilburn, M. Coakley, M. Beaney, L. Fox, K. Goddard, I. Garcia-Murillas, P. Proszek, P. Hall, C. Harper-Wynne, T. Hickish, S. Kernaghan, I. R. Macpherson, A. F. C. Okines, C. Palmieri, S. Perry, K. Randle, C. Snowdon, H. Stobart, A. M. Wardley, D. Wheatley, S. Waters, M. C. Winter, M. Hubank, S. D. Allen, J. M. Bliss
Summary: The c-TRAK TN study is the first prospective study to evaluate the clinical utility of ctDNA testing in guiding therapy in TNBC. It found that TNBC patients had a high rate of metastatic disease on ctDNA detection. These findings have important implications for future trial design, emphasizing the importance of starting ctDNA testing early and using more sensitive and/or frequent ctDNA testing regimes.
ANNALS OF ONCOLOGY
(2023)
Review
Immunology
Victoria Male, Ashley Moffett
Summary: The presence of granulated lymphocytes known as uNK cells in the human uterine mucosa was first noted in the nineteenth century, but they were identified as a type of NK cell in 1990. Uterine NK cells have been found to be less cytotoxic than their peripheral counterparts. Recent research has identified three subpopulations of uNK cells that cluster separately from peripheral NK cells. This review examines the history of uNK cell research, their interactions with placental cells, their role in placental implantation, and their potential for defending against infection and mediating memory effects.
ANNUAL REVIEW OF IMMUNOLOGY
(2023)
Article
Oncology
Elizabeth J. Harvey-Jones, Christopher J. Lord, Andrew N. J. Tutt
Summary: Treatment options for hereditary breast cancer patients have greatly expanded in the past 20 years, including the FDA-licensed olaparib which improves overall survival in patients with gBRCA1/2 mutations. However, resistance to platinum-based chemotherapy and PARPi is a significant issue for these patients.
HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA
(2023)
Article
Multidisciplinary Sciences
Jennifer Cable, Kenneth W. Witwer, Robert J. Coffey, Aleksandar Milosavljevic, Ariana K. von Lersner, Lizandra Jimenez, Ferdinando Pucci, Maureen M. Barr, Niek Dekker, Bahnisikha Barman, Daniel Humphrys, Justin Williams, Michele de Palma, Wei Guo, Nuno Bastos, Andrew F. Hill, Efrat Levy, Michael P. Hantak, Clair Crewe, Elena Aikawa, Alan M. Adamczyk, Tamires M. Zanotto, Matias Ostrowski, Tanina Arab, Daniel C. Rabe, Aadil Sheikh, Danilo Rodrigues da Silva, Jennifer C. Jones, Chioma Okeoma, Thomas Gaborski, Qin Zhang, Olesia Gololobova
Summary: Extracellular vesicles (EVs) are small particles released by cells that carry important biomolecules and can act as messengers to coordinate tissue homeostasis and systemic responses. EVs are of growing interest for their potential as diagnostic biomarkers and drug-delivery vehicles. Researchers gathered at the Keystone symposium to discuss standardized language and methodology, new data on EV biology and clinical utility, and novel technologies for EV isolation and characterization.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Oncology
E. Jamshidi, A. Asgary, S. Setareh, A. Casutt, M. Gonzalez, M. P. Bianchi, A. Lovis, M. De Palma, C. von Garnier, N. Mansouri
Summary: Using machine learning techniques, this study investigated the correlations between medical and personal characteristics of cancer patients and the risk of lung metastasis, leading to potential improvements in clinical management and outcomes. The study identified obesity, advanced age, and underlying lung disease as strong predictors for lung metastasis. The predictive model developed in this study can assist physicians in preventive risk factor control and treatment strategies.
Editorial Material
Cell Biology
Victoria Male
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Licun Wu, Mikihiro Kohno, Junichi Murakami, Amin Zia, Jonathan Allen, Hana Yun, Meilin Chan, Cristina Baciu, Mingyao Liu, Veronique Serre-Beinier, Michele De Palma, Emanuela Felley-Bosco, Jonathan Yeung, Trevor J. Pugh, Marc de Perrot
Summary: Defining the origin of tumor-associated macrophages (TAM) is crucial for developing targeted therapies for mesothelioma. Two distinct macrophage populations, small peritoneal/pleural macrophages (SPM) and large peritoneal/pleural macrophages (LPM), were identified in mice. SPM, which mainly consisted of M2-like TAM, rapidly increased in the tumor microenvironment and contributed to tumor development. On the other hand, LPM activated the IFN-gamma response and played a crucial role in the immune response, as confirmed by their depletion leading to loss of antitumoral memory immunity. The gene signature of SPM was observed in the pleural effusion and tumor of untreated mesothelioma patients, suggesting potential therapeutic targets.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Oncology
Hideko Yamauchi, Masakazu Toi, Shin Takayama, Seigo Nakamura, Toshimi Takano, Karen Cui, Christine Campbell, Liesbet De Vos, Charles Geyer Jr, Andrew Tutt
Summary: This study compared the efficacy and safety of olaparib with placebo in a subset of patients from Japan. The results showed that olaparib was as effective and safe in improving patient outcomes as it was in the global OlympiA population, suggesting its applicability in clinical practice in Japan.
Review
Oncology
Mengyuan Li, Angela Quintana, Elena Alberts, Miu Shing Hung, Victoire Boulat, Merce Marti Ripoll, Anita Grigoriadis
Article
Oncology
Holly Tovey, Orsolya Sipos, Joel S. Parker, Katherine A. Hoadley, Jelmar Quist, Sarah Kernaghan, Lucy Kilburn, Roberto Salgado, Sherene Loi, Richard D. Kennedy, Ioannis Roxanis, Patrycja Gazinska, Sarah E. Pinder, Judith Bliss, Charles M. Perou, Syed Haider, Anita Grigoriadis, Andrew Tutt, Maggie Chon U. Cheang
Summary: This study explored the predictive ability of DNA damage response (DDR) and immune markers in the treatment response of triple-negative breast cancer. High immune features predict response to docetaxel, while high DDR signature scores predict response to carboplatin. Patients can be divided into different subgroups based on their treatment sensitivity. Caution is needed when using transcriptional signatures derived from primary tumors to guide treatment.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Joseph S. Baxter, Rachel Brough, Dragomir B. Krastev, Feifei Song, Sandhya Sridhar, Aditi Gulati, John Alexander, Theodoros I. Roumeliotis, Zuza Kozik, Jyoti S. Choudhary, Syed Haider, Stephen J. Pettitt, Andrew N. J. Tutt, Christopher J. Lord
Summary: The synthetic lethal effects of FBXW7 have been identified, which could serve as a starting point for further drug discovery and development in this area.
MOLECULAR ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Stephen J. Pettitt, Nan Shao, Diana Zatreanu, Jessica Frankum, Ilirjana Bajrami, Rachel Brough, Dragomir B. Krastev, Theodoros I. Roumeliotis, Jyoti S. Choudhary, Sonja Lorenz, Alistair Rust, Johann S. de Bono, Timothy A. Yap, Andrew N. J. Tutt, Christopher J. Lord
Summary: Reduced expression of HUWE1 leads to increased levels of BRCA1- increment 11q and PARPi resistance. This effect is specific to cells able to express BRCA1- increment 11q and is not seen in other BRCA1 or BRCA2 mutant cells. HUWE1 silencing also restores RAD51 nuclear foci and platinum salt resistance, indicating its potential as a biomarker for PARPi resistance in future clinical trials.
Article
Oncology
Hannah Si Hui Lau, Veronique Kiak Mien Tan, Benita Kiat Tee Tan, Yirong Sim, Jelmar Quist, Aye Aye Thike, Puay Hoon Tan, Shazib Pervaiz, Anita Grigoriadis, Kanaga Sabapathy
Summary: This study reveals the regional heterogeneity in both tumors and peri-tumoral stroma of invasive breast carcinomas, providing insights into the importance of peri-tumoral heterogeneity in the evolution and treatment of breast cancers. A pro-inflammatory adipose-enriched peri-tumoral subtype is identified, which is significantly associated with poorer overall survival in breast cancer patients.
Article
Immunology
Ee Von Woon, Dimitrios Nikolaou, Kate MacLaran, Julian Norman-Taylor, Priya Bhagwat, Antonia O. O. Cuff, Mark R. R. Johnson, Victoria Male
Summary: A significant proportion of unexplained reproductive failure is associated with immunological dysfunction at the maternal-fetal interface. Uterine Natural Killer cells (uNK) play a crucial role in successful pregnancy by regulating EVT invasion and spiral artery remodeling. This study explores the frequency, phenotype, and function of uNK subsets in women with unexplained reproductive failure and reveals a global reduction in expression of uNK receptors important for interaction with HLA-C and HLA-G, leading to reduced uNK activation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Ali Ghasemi, Amaia Martinez-Usatorre, Luqing Li, Mehdi Hicham, Alan Guichard, Rachel Marcone, Nadine Fournier, Bruno Torchia, Darel Martinez Bedoya, Suzel Davanture, Mirian Fernandez-Vaquero, Chaofan Fan, Jakob Janzen, Yahya Mohammadzadeh, Raphael Genolet, Nahal Mansouri, Mathias Wenes, Denis Migliorini, Mathias Heikenwalder, Michele De Palma
Summary: This study develops a dendritic cell therapy by using dendritic cell progenitors engineered to produce IL-12 and FLT3L, showing antigen-agnostic reduction of tumor burden that can be exploited for combination therapy in glioma.
