Article
Genetics & Heredity
Kevin Nee, Dennis Ma, Quy H. Nguyen, Maren Pein, Nicholas Pervolarakis, Jacob Insua-Rodriguez, Yanwen Gong, Grace Hernandez, Hamad Alshetaiwi, Justice Williams, Maha Rauf, Kushal Rajiv Dave, Keerti Boyapati, Aliza Hasnain, Christian Calderon, Anush Markaryan, Robert Edwards, Erin Lin, Ritesh Parajuli, Peijie Zhou, Qing Nie, Sundus Shalabi, Mark A. LaBarge, Kai Kessenbrock
Summary: Premalignant stromal cells from women with germline BRCA1 mutations have increased expression of secreted factors regulating epithelial homeostasis, promoting premalignant epithelial changes and increased breast cancer risk. The stromal niche in BRCA1-driven tumor initiation promotes epithelial proliferation and mutant BRCA1-driven tumorigenesis through paracrine signals, such as matrix metalloproteinase 3 (MMP3), produced by pre-cancer-associated fibroblasts (pre-CAFs). This study highlights the importance of precancerous stroma in BRCA1(+/mut) in elevating breast cancer risk.
Article
Cell Biology
Beiping Zhong, Bing Cheng, Xiaoming Huang, Qian Xiao, Zhitong Niu, Yu-feng Chen, Qiang Yu, Wenyu Wang, Xiao-Jian Wu
Summary: Cancer-associated fibroblasts (CAFs) play a crucial role in colorectal cancer (CRC) metastasis by inducing the expression of Leucine Rich Alpha-2-Glycoprotein 1 (LRG1), which promotes CRC migration and invasion through epithelial-mesenchymal transition (EMT). The CAFs-mediated IL-6-STAT3-LRG1 axis is responsible for the up-regulation of LRG1 in CRC, and higher LRG1 expression predicts poor clinical outcomes, especially distant metastasis free survival in CRC patients.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Barnabas Irmer, Janes Efing, Lea Elisabeth Reitnauer, Allegra Angenendt, Saskia Heinrichs, Antonia Schubert, Matthias Schulz, Claudia Binder, Joke Tio, Uwe Hansen, Christiane Geyer, Mirjam Gerwing, Annalen Bleckmann, Kerstin Menck
Summary: EVs can transfer oncogenic Wnt receptors ROR1/2 to the surface of ROR-negative cancer cells, inducing an aggressive phenotype that supports tumor progression. This transfer was observed both in vitro and in vivo, and ROR-positive EVs were also found to be significantly elevated in the plasma of breast cancer patients.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Medicine, Research & Experimental
Iolanda Scognamiglio, Lorenza Cocca, Ilaria Puoti, Francesco Palma, Francesco Ingenito, Cristina Quintavalle, Alessandra Affinito, Giuseppina Roscigno, Silvia Nuzzo, Rosario Vincenzo Chianese, Stefania Belli, Guglielmo Thomas, Timo Schomann, Alan Chan, Maria Patrizia Stoppelli, Gerolama Condorelli
Summary: Research has shown that exosomes derived from triple-negative breast cancer cells can activate normal fibroblasts and transform them into cancer-associated fibroblasts, thereby promoting tumor invasion. These findings highlight the significant role of breast cancer cells in remodeling the tumor microenvironment and contributing to tumor evolution.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Biochemistry & Molecular Biology
Ramesh Butti, Ramakrishna Nimma, Gautam Kundu, Anuradha Bulbule, Totakura V. S. Kumar, Vinoth Prasanna Gunasekaran, Deepti Tomar, Dhiraj Kumar, Anupama Mane, Satyajit S. Gill, Tushar Patil, Georg F. Weber, Gopal C. Kundu
Summary: This study reveals the crosstalk between cancer cells and stromal fibroblasts that drives tumor progression. Tumor cells stimulate fibroblasts to differentiate into myofibroblasts by secreting OPN, which in turn secrete CXCL12 to promote epithelial to mesenchymal transition in tumor cells.
Article
Engineering, Biomedical
Eric Parigoris, Soojung Lee, David Mertz, Madeleine Turner, Amy Y. Liu, Jason Sentosa, Sabra Djomehri, Hao Chen Chang, Kathryn Luker, Gary Luker, Celina G. Kleer, Shuichi Takayama
Summary: This study describes mammary organoids with a basal-in phenotype, achieved through specific material considerations and co-culture of cells, showing self-organization of cancer and epithelial cells inside the organoid. It was found that invasion of tumor cells is more prominent in organoids with less developed basement membranes compared to those with more defined ones.
ADVANCED HEALTHCARE MATERIALS
(2021)
Article
Cell Biology
Baochi Ou, Yuan Liu, Xiaowei Yang, Xiaojun Xu, Yunwen Yan, Jingjie Zhang
Summary: A novel subset of C5aR1-positive neutrophils inducing breast cancer glycolysis through ERK1/2-WTAP-dependent m6A methylation of ENO1 has been discovered. These neutrophils are associated with tumor growth and poor prognosis in breast cancer patients.
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Mokarram Hossain, Raymond Shim, Woo-Yong Lee, Arlene H. Sharpe, Paul Kubes
Summary: Emerging evidence suggests that resident macrophages within tissues play a role in tumor growth. In this study, the authors discovered that GATA6(+) large peritoneal macrophages can invade growing metastases in the liver and promote tumor growth.
NATURE COMMUNICATIONS
(2022)
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
Oncology
Zhuo Chen, Jing Wu, Liang Wang, Hua Zhao, Jie He
Summary: The study reveals that M2-tumor associated macrophages (TAMs) are more abundant in TNBC and associated with poor prognosis. M2-TAMs promote invasion, migration, and proliferation of breast cancer cells, possibly through the mechanism of epithelial-mesenchymal transition.
Article
Oncology
Jia-Shing Chen, Yu-Ning Teng, Cheng-Yi Chen, Jing-Yi Chen
Summary: This study revealed a non-canonical molecular mechanism of IL-6 upregulating KDM2A expression in CAFs via a novel STAT3/NF kappa B p50 axis. KDM2A-expressing CAFs predominantly secreted CXCR2-associated chemokines to promote M2 macrophage polarization and enhance paclitaxel resistance in breast cancer, suggesting the therapeutic potential of targeting the CXCR2 or CCR2 pathway for paclitaxel-resistant breast cancer.
CANCER CELL INTERNATIONAL
(2023)
Article
Cell Biology
Fangzhou Ye, Yiran Liang, Yajie Wang, Robert Le Yang, Dan Luo, Yaming Li, Yuhan Jin, Dianwen Han, Bing Chen, Wenjing Zhao, Lijuan Wang, Xi Chen, Tingting Ma, Xiaoli Kong, Qifeng Yang
Summary: Breast cancer is a common malignancy and exosome-mediated communication between cancer-associated fibroblasts (CAFs) and breast cancer cells plays a role in tumor progression. This study identified circTBPL1 as an upregulated circRNA in exosomes derived from CAFs. Transfer of exosomal circTBPL1 from CAFs to breast cancer cells promoted cell proliferation, migration, and invasion. Further investigation revealed that circTBPL1 acts as a sponge for miR-653-5p, leading to increased expression of TPBG and enhanced breast cancer progression. These findings suggest that exosomal circTBPL1 could serve as a biomarker and therapeutic target for breast cancer.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Balaji Virassamy, Franco Caramia, Peter Savas, Sneha Sant, Jianan Wang, Susan N. Christo, Ann Byrne, Kylie Clarke, Emmaline Brown, Zhi Ling Teo, Bianca von Scheidt, David Freestone, Luke C. Gandolfo, Karsten Weber, Julia Teply-Szymanski, Ran Li, Stephen J. Luen, Carsten Denkert, Sibylle Loibl, Olivia Lucas, Charles Swanton, Terence P. Speed, Phillip K. Darcy, Paul J. Neeson, Laura K. Mackay, Sherene Loi
Summary: CD8+ tumor-infiltrating lymphocytes with a tissue-resident memory T (TRM) cell phenotype are associated with favorable prognosis in triple-negative breast cancer (TNBC). The study shows that intratumoral CD8+ T cells in mice and TNBC patients transcriptionally resemble each other. Two intratumoral sub-populations were identified, one with markers of terminal exhaustion (TEX-like) and the other with a bona fide resident phenotype (TRM-like). Treatment with checkpoint inhibitors resulted in expansion of the TRM-like subset with enhanced cytotoxic capacity and improved clinical outcomes in TNBC patients.
Article
Cell Biology
Wen Jia, Mohit Kumar Jolly, Herbert Levine
Summary: The epithelial-mesenchymal transition (EMT) is a crucial cellular process for wound healing, cancer metastasis, and embryonic development. Recent studies have shown that hybrid epithelial/mesenchymal states, possessing both epithelial and mesenchymal traits, play a significant role in cancer metastasis and resistance to therapies. NRF2 has been identified as a stabilizing factor for these hybrid states. This research incorporates a phenomenological epigenetic feedback effect into a computational model for EMT signaling and demonstrates its stabilizing effect on the hybrid state if NRF2 influences SNAIL at an epigenetic level.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Abibatou Ndoye, Rakshitha Pandulal Miskin, C. Michael DiPersio
Summary: The study reveals a critical role for integrin alpha 3 beta 1 in promoting breast cancer cell invasion by repressing the expression of Reelin, suggesting its potential as a therapeutic target for breast cancer treatment.
Article
Health Care Sciences & Services
John N. Primrose, Sian A. Pugh, Gareth Thomas, Matthew Ellis, Karwan Moutasim, David Mant
Summary: This study aimed to use intratumoural immune signature to identify a subgroup of colorectal cancer patients with a very low relapse rate, thus reducing unnecessary follow-ups. However, due to hardware and software issues, as well as the loss of critical scientific staff, reliable data could not be obtained within the study timeframe, resulting in failure to achieve the original project goal.
HEALTH TECHNOLOGY ASSESSMENT
(2021)
Review
Oncology
Laura D. Wood, Andrew J. Ewald
Summary: The use of three-dimensional culture models, especially organoids, has greatly expanded in cancer research, providing valuable tools for studying cellular strategies and molecular mechanisms driving cancer initiation and progression. Organoids can be used for short-term acute cultures or long-term studies, and offer advantages in addressing specific research questions in cancer biology.
JOURNAL OF PATHOLOGY
(2021)
Article
Multidisciplinary Sciences
Helen R. Clark, Connor McKenney, Nathan M. Livingston, Ariel Gershman, Seema Sajjan, Isaac S. Chan, Andrew J. Ewald, Winston Timp, Bin Wu, Abhyudai Singh, Sergi Regot
Summary: Epithelial tissues respond to microbial patterns in a digital manner, activating a subset of cells through regulation of a bimodal epigenetic switch. Epigenetic licensing in individual cells allows for long-term, quantitative fine-tuning of population-level responses. Fine tuning the immune response according to the threat level is crucial for distinguishing between pathogens and commensal bacteria.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Akshay Narkar, Blake A. Johnson, Pandurang Bharne, Jin Zhu, Veena Padmanaban, Debojyoti Biswas, Andrew Fraser, Pablo A. Iglesias, Andrew J. Ewald, Rong Li
Summary: Studies suggest that p53 may not serve as a universal surveillance factor restricting the proliferation of aneuploid cells, but instead play a role in ensuring faithful chromosome transmission likely by preventing polyploidization and influencing spindle mechanics, both directly or indirectly.
Article
Engineering, Biomedical
Chia-Yi Su, Alice Burchett, Matthew Dunworth, Jong Seob Choi, Andrew J. Ewald, Eun Hyun Ahn, Deok-Ho Kim
Summary: A new 3D tumor model has been developed to recapitulate the response of tumors to different ECM structures and simulate tumor invasion through guided fiber alignment. This model provides a new tool for studying collective tumor invasion and holds potential for discovering therapeutic agents targeted against cancer invasion.
Article
Cell Biology
Stephanie Torrino, Eloise M. Grasset, Stephane Audebert, Ilyes Belhadj, Caroline Lacoux, Meagan Haynes, Sabrina Pisano, Sophie Abelanet, Frederic Brau, Stephen Y. Chan, Bernard Mari, William M. Oldham, Andrew J. Ewald, Thomas Bertero
Summary: In this study, it was found that breast cancer cells respond to mechanical signals by rewiring glutamine metabolism to promote microtubule glutamylation and enhance microtubule stability, thereby promoting cell invasion. Inhibition of glutamine metabolism affects microtubule stability, while reducing microtubule glutamylation weakens cancer aggressiveness.
Article
Immunology
Simon Eschweiler, James Clarke, Ciro Ramirez-Suastegui, Bharat Panwar, Ariel Madrigal, Serena J. Chee, Ioannis Karydis, Edwin Woo, Aiman Alzetani, Somaia Elsheikh, C. J. Hanley, G. J. Thomas, Peter S. Friedmann, Tilman Sanchez-Elsner, Ferhat Ay, Christian H. Ottensmeier, Pandurangan Vijayanand
Summary: Studies have shown the importance of T-FR cells within tumor tissues in enhancing the efficacy of anti-PD-1 therapy. Depleting or blocking T-FR cells can improve the effectiveness of anti-PD-1 treatment and contribute to better survival outcomes in melanoma patients.
Article
Oncology
Hetakshi Kurani, Seyedeh Fatemeh Razavipour, Kuzhuvelil B. Harikumar, Matthew Dunworth, Andrew J. Ewald, Apsra Nasir, Gray Pearson, Derek Van Booven, Zhiqun Zhou, Diana Azzam, Claes Wahlestedt, Joyce Slingerland
Summary: This study identified DOT1L as a key regulator of cancer stem cells (CSCs) in triple-negative breast cancer (TNBC). Inhibition of DOT1L suppressed the growth and metastasis of TNBC CSCs, suggesting that DOT1L inhibitors may be a potential therapeutic option for targeting stem cell-enriched TNBC.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Hillary Stires, Igor Bado, Thelma Brown, Martha Carlson, Isaac S. Chan, Gloria V. Echeverria, Andrew J. Ewald, Bora Lim, Carla Lloyd, Julia Maues, Steffi Oesterreich, Robert N. Riter, Kelly Shanahan, Alana L. Welm, Josh Newby
Summary: Incorporating patient advocates into basic cancer research can enhance research intentionality, effective communication, and direct connections between researchers and those they aim to help. However, many cancer research scientists do not collaborate with patient advocates. Through hosting workshops and discussing findings at an international conference, we identified barriers and provided actionable steps to support researchers in working with patient advocates to improve cancer research and achieve our collective goal.
Article
Oncology
Massimiliano Mellone, Klaudia Piotrowska, Giulia Venturi, Lija James, Aleksandra Bzura, Maria A. Lopez, Sonya James, Chuan Wang, Matthew J. Ellis, Christopher J. Hanley, Josephine F. Buckingham, Kerry L. Cox, Gareth Hughes, Viia Valge-Archer, Emma King, Stephen A. Beers, Vincent Jaquet, George D. D. Jones, Natalia Savelyeva, Emre Sayan, Jason L. Parsons, Stephen Durant, Gareth J. Thomas
Summary: Myofibroblastic cancer-associated fibroblast (myoCAF)-rich tumors have low T cell infiltration and poor response to immune-checkpoint blockade. This study identifies ATM as a central regulator of myoCAF differentiation, providing a potential therapeutic target for overcoming immunotherapy resistance in myoCAF-rich tumors.
Article
Cell Biology
Neil M. Neumann, Daniel M. Kim, Robert J. Huebner, Andrew J. Ewald
Summary: In this study, the process of bifurcation of mammary epithelium was investigated. The researchers observed changes in cell migration speed and the role of TGF-0 signaling in this process, revealing the mechanism behind mammary epithelial bifurcation.
JOURNAL OF CELL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Elodie Henriet, Hildur Knutsdottir, Eloise M. M. Grasset, Matthew Dunworth, Meagan Haynes, Joel S. S. Bader, Andrew J. J. Ewald
Summary: Inter-patient and intra-tumoral heterogeneity makes it difficult to identify predictive biomarkers and effective treatments for basal triple negative breast cancer (b-TNBC). In this study, we cultured organoids from a b-TNBC mouse model and characterized their invasive behavior. By isolating individual organoids from collagen gels based on invasive morphology and performing RNA sequencing, we identified KRAS and ERK as essential regulators of collective and single cell dissemination. Inhibition of EGFR, MAPK/ERK, or PI3K/AKT signaling was found to reduce invasion.
Article
Multidisciplinary Sciences
Christopher J. Hanley, Sara Waise, Matthew J. Ellis, Maria A. Lopez, Wai Y. Pun, Julian Taylor, Rachel Parker, Lucy M. Kimbley, Serena J. Chee, Emily C. Shaw, Jonathan West, Aiman Alzetani, Edwin Woo, Christian H. Ottensmeier, Matthew J. J. Rose-Zerilli, Gareth J. Thomas
Summary: Through single cell RNA-sequencing, multiplexed immunohistochemistry, and digital cytometry, three major fibroblast subpopulations in non-small cell lung cancer are identified and characterised. These subpopulations include adventitial, alveolar, and myofibroblasts. Myofibroblasts are associated with poor overall survival rates in lung adenocarcinomas, while their presence in squamous carcinomas does not have a prognostic value. These findings have important implications for the development of fibroblast-targeting strategies in cancer therapy.
NATURE COMMUNICATIONS
(2023)
Review
Medicine, Research & Experimental
Isaac S. Chan, Andrew J. Ewald
Summary: NK cells play a critical role in the body's defense against tumors and metastasis. Recent research has examined the interaction between metastatic cancer cells and NK cells. The unique biology of cancer cells at each stage of metastasis alters the fundamental biology of NK cells, including the ability of cancer cells to evade immune surveillance and manipulate NK cells to promote metastasis. This knowledge has potential translational applications in medicine.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Dentistry, Oral Surgery & Medicine
Kamila J. Bienkowska, Christopher J. Hanley, Gareth J. Thomas
Summary: The role of cancer-associated fibroblasts (CAF) in the microenvironment of oral cancer (OSCC) is crucial for promoting cancer progression and resistance to therapy. CAF with an activated myofibroblastic phenotype support OSCC progression and confer resistance to immuno- and targeted therapies, leading to poor prognosis in CAF-rich OSCC. Additionally, CAF shield tumors from immune attack through multiple mechanisms, particularly in promoting resistance to anti-PD-1/PD-L1 checkpoint inhibitors.
FRONTIERS IN ORAL HEALTH
(2021)