Article
Oncology
Mayuko Kawata, Jumpei Kondo, Kunishige Onuma, Yu Ito, Takeshi Yokoi, Junzo Hamanishi, Masaki Mandai, Tadashi Kimura, Masahiro Inoue
Summary: This study investigated the role of apicobasal polarity in peritoneal dissemination of ovarian cancer using patient-derived organoids. The findings suggest that SRC kinase-mediated polarity switching is involved in peritoneal metastasis, highlighting its potential as a therapeutic target.
Article
Oncology
Adam L. Burrack, Ellen J. Spartz, Meagan R. Rollins, Ebony A. Miller, Maria Firulyova, Eduardo Cruz, Michael F. Goldberg, Iris X. Wang, Hezkiel Nanda, Steven Shen, Konstantin Zaitsev, Ingunn M. Stromnes
Summary: Pancreatic ductal adenocarcinoma (PDA) is a lethal and metastatic malignancy resistant to therapy. Understanding the differentiation and maintenance of tumor-specific T cells in vivo can lead to innovative therapeutic strategies. The spleen harbors tumor-specific CD8 T cells that can be functionally distinguished based on Cxcr3 and Klrg1 expression. Cxcr3+ Klrg1- T cells possess stem cell-like properties, while Cxcr3-Klrg1+ T cells display characteristics of terminal differentiation. Intermediate Cxcr3+ Klrg1+ T cells in the spleen are highly enriched for tumor specificity. However, tumor-specific T cells infiltrating primary tumors lose Cxcr3 and Klrg1 expression and upregulate exhaustion markers PD-1 and Lag-3. The absence of Cxcr3 enhances IFN gamma production in primary tumors but facilitates cancer cell dissemination, emphasizing the importance of Cxcr3 in controlling metastasis. Intratumoral myeloid cells and splenic DC subsets differentially produce chemokines Cxcl10 and Cxcl9 following immunotherapy, influencing T cell differentiation. Overall, Cxcr3 influences peripheral T cell fate rather than intratumoral T cell trafficking, thereby mitigating tumor cell dissemination.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Review
Immunology
Martin Kolev, Madhumita Das, Monica Gerber, Scott Baver, Pascal Deschatelets, Maciej M. Markiewski
Summary: Recent studies have shown that complement plays a role in accelerating cancer progression by suppressing antitumor immunity in the tumor microenvironment. Activation of intracellular complement is crucial for the survival of immune cells, making it important for tumor cell survival and growth. Additionally, intracellular complement activation is essential for priming antitumor T cell responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, General & Internal
Lucia Borriello, John Condeelis, David Entenberg, Maja H. Oktay
Summary: The research found that breast cancer cells can disseminate not only from primary tumors and metastatic nodules in the lymph nodes to distant organs, but also from lung metastases. Re-dissemination of cancer cells could be a crucial mechanism leading to overt metastases and patient demise.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Medicine, General & Internal
Ioannis A. Voutsadakis
Summary: Alterations in the planar cell polarity (PCP) pathway genes can be observed in breast cancers, particularly in the basal subtype. Two breast cancer cell line models with amplifications in PCP genes display sensitivity to inhibitors of acyl-transferase porcupine, suggesting these inhibitors may be potential candidates for combination therapy in PCP-altered breast cancers.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Kazuya Tsujita, Reiko Satow, Shinobu Asada, Yoshikazu Nakamura, Luis Arnes, Keisuke Sako, Yasuyuki Fujita, Kiyoko Fukami, Toshiki Itoh
Summary: Changes in cell mechanics contribute to cancer cell dissemination. High plasma membrane (PM) tension inhibits cancer dissemination by counteracting mechanosensitive BAR family protein assembly, while restoration of PM tension phenotypically convert malignant cells into a non-motile epithelial cell state.
NATURE COMMUNICATIONS
(2021)
Review
Immunology
Saeed Asiry, Gina Kim, Panagiota S. Filippou, Luis Rivera Sanchez, David Entenberg, Douglas K. Marks, Maja H. Oktay, George S. Karagiannis
Summary: The dissemination trajectories, serving as immune deserts, provide transient and localized immunosubversion cues to migratory/invasive cancer cell subpopulations, enabling them to efficiently evade immunological destruction and seed metastatic sites. A deeper understanding of the molecular and cellular composition of these trajectories will aid in the development of new therapeutic strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Alvin Ho-Kwan Cheung, Chris Ho-Lam Hui, Kit Yee Wong, Xiaoli Liu, Bonan Chen, Wei Kang, Ka Fai To
Summary: The use of cell cycle inhibitors in tumor biology has highlighted the importance of understanding the cell cycle for optimizing therapeutic approaches. Cell cycle aberrations in cancers have been found to have oncogenic effects beyond cell proliferation alone, impacting cancer metabolism, immunity, and metastasis. This review comprehensively summarizes recent findings and advances in these interrelated processes, emphasizing knowledge gaps, therapeutic approaches, and challenges in targeted therapy resistance. Understanding how the cell cycle modulates diverse aspects of cancer biology is crucial for identifying new molecular targets.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Cell Biology
Jacob P. Veenstra, Lucas Felipe Fernandes Bittencourt, Katherine M. Aird
Summary: Ovarian cancer is a highly aggressive disease, often diagnosed late after it has spread. Inflammatory signals and cellular senescence play important roles in ovarian cancer dissemination. Recent studies have shown that platinum-based or PARP inhibitor therapies, standard treatments for ovarian cancer, can induce senescence in ovarian cancer cells, leading to an inflammatory response known as the senescence-associated secretory phenotype (SASP). The SASP may promote metastasis in ovarian cancer.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Review
Cell Biology
Samantha George, Joshua Alexander James Martin, Vittoria Graziani, Victoria Sanz-Moreno
Summary: Cell migration plays a crucial role in immune responses and cancer metastasis. Amoeboid migrating cells use myosin II-powered blebs to move and change their shape and direction. Both immune cells and metastatic cancer cells utilize amoeboid migration, but with different purposes and processes. Exploring the similarities and differences between amoeboid immune and cancer cells can enhance our understanding of metastasis and provide insights for targeted therapies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Cell Biology
Jungsun Kim
Summary: Pancreatic cancer is characterized by high recurrence rate and low survival rate. Surgery is the most effective treatment, but most patients experience recurrence after surgery. Subclinical dormant pancreatic cancer cells are believed to disseminate before developing metastatic or recurring cancer, and there are multiple routes and mechanisms involved in pancreatic cancer migration and adaptation.
Article
Biochemistry & Molecular Biology
Chaoyi Chen, Hongfei Yu, Fengyan Han, Xuan Lai, Kehong Ye, Siqin Lei, Minglang Mai, Maode Lai, Honghe Zhang
Summary: The study reveals that circRHOBTB3 is upregulated in serum and downregulated in tissue samples of CRC patients, with the downregulation associated with poor prognosis. CircRHOBTB3 acts as a tumor suppressor by repressing metabolic pathways and intracellular ROS production. SNF8 is identified as the protein responsible for sorting circRHOBTB3 into exosomes, and CRC cells secrete more circRHOBTB3 compared to normal cells. Antisense oligonucleotides targeting regulatory elements of circRHOBTB3 can increase its expression and inhibit its exosomal secretion, thereby inhibiting CRC growth and metastasis.
Article
Multidisciplinary Sciences
Matteo Rossi, Patricia Altea-Manzano, Margherita Demicco, Ginevra Doglioni, Laura Bornes, Marina Fukano, Anke Vandekeere, Alejandro M. Cuadros, Juan Fernandez-Garcia, Carla Riera-Domingo, Cristina Jauset, Melanie Planque, H. Furkan Alkan, David Nittner, Dongmei Zuo, Lindsay A. Broadfield, Sweta Parik, Antonino Alejandro Pane, Francesca Rizzollo, Gianmarco Rinaldi, Tao Zhang, Shao Thing Teoh, Arin B. Aurora, Panagiotis Karras, Ines Vermeire, Dorien Broekaert, Joke Van Elsen, Maximilian M. L. Knott, Martin F. Orth, Sofie Demeyer, Guy Eelen, Lacey E. Dobrolecki, Ayse Bassez, Thomas Van Brussel, Karl Sotlar, Michael T. Lewis, Harald Bartsch, Manfred Wuhrer, Peter van Veelen, Peter Carmeliet, Jan Cools, Sean J. Morrison, Jean-Christophe Marine, Diether Lambrechts, Massimiliano Mazzone, Gregory J. Hannon, Sophia Y. Lunt, Thomas G. P. Grunewald, Morag Park, Jacco van Rheenen, Sarah-Maria Fendt
Summary: The loss of phosphoglycerate dehydrogenase (PHGDH) has been found to increase cancer metastasis. Heterogeneous or low expression of PHGDH in primary tumors of breast cancer patients is associated with decreased metastasis-free survival time. Loss of PHGDH activates the hexosamine-sialic acid pathway through its interaction with the glycolytic enzyme phosphofructokinase, leading to increased cell migration and invasion.
Review
Oncology
Anna Szczerba, Aleksandra Sliwa, Pawel P. Pieta, Anna Jankowska
Summary: This review focuses on the biology of ovarian circulating tumor cells (CTCs) and their role in the diagnosis and therapy of ovarian cancer.
Article
Oncology
Meri Rogava, Andreas Dominik Braun, Tetje Cornelia van der Sluis, Naveen Shridhar, Thomas Tueting, Evelyn Gaffal
Summary: This study demonstrates the important role of TLR4 in the progression and metastatic spread of melanoma cells, finding that melanoma cells lacking functional TLR4 show increased sensitivity to cell killing induced by tumor necrosis factor alpha and significantly reduced ability to metastasize to the lungs. Activation of TLR4 also promotes migration in a subset of human melanoma cell lines, highlighting TLR4 as a potential target for therapeutic inhibition in melanoma.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Cell Biology
Orit Katarina Sirka, Eliah R. Shamir, Andrew J. Ewald
JOURNAL OF CELL BIOLOGY
(2018)
Article
Oncology
Dan Georgess, Veena Padmanaban, Orit Katarina Sirka, Kester Coutinho, Alex Choi, Gabriela Frid, Neil M. Neumann, Takanari Inoue, Andrew J. Ewald
Article
Oncology
Vanesa L. Silvestri, Elodie Henriet, Raleigh M. Linville, Andrew D. Wong, Peter C. Searson, Andrew J. Ewald
Article
Biochemical Research Methods
Veena Padmanaban, Eloise M. Grasset, Neil M. Neumann, Andrew K. Fraser, Elodie Henriet, William Matsui, Phuoc T. Tran, Kevin J. Cheung, Dan Georgess, Andrew J. Ewald
Article
Oncology
Christopher J. Hanley, Elodie Henriet, Orit Katarina Sirka, Gareth J. Thomas, Andrew J. Ewald
MOLECULAR CANCER RESEARCH
(2020)
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
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
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.
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)
