Article
Biochemistry & Molecular Biology
Fan Yang, Lu Yuan, Minghui Xiang, Qiang Jiang, Manling Zhang, Fanghui Chen, Jie Tong, Jinming Huang, Yafei Cai
Summary: The mammary gland epithelium plays a crucial role in the innate immunity of the bovine mammary gland. This study found that there is a high correlation and direct interaction between TLR4 and SYK in mastitis mammary epithelium. In addition, it was discovered that SYK can inhibit the inflammatory response caused by infection. These findings reveal the role of the TLR4/SYK/NF-kappa B signaling axis in regulating innate immunity response in bovine mammary epithelial cells.
Article
Biochemistry & Molecular Biology
Lilia Sanchez, Jessica Epps, Steven Wall, Cole McQueen, Scott J. Pearson, Kelly Scribner, Elizabeth A. Wellberg, Erin D. Giles, Monique Rijnkels, Weston W. Porter
Summary: The functionally differentiated mammary gland adapts to extreme levels of stress by activating specific protective mechanisms. The breast tumor suppressor gene SIM2s is identified as a novel regulator of mitophagy, a key component of this stress response.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Agriculture, Dairy & Animal Science
Laura Lopez-Diez, Camilo Calle-Velasquez, Mark D. Hanigan, Zulma Tatiana Ruiz-Cortes
Summary: The study highlights the ability of mammary gland cells to maintain stable levels of casein despite reduced essential amino acid supply, potentially leading to more efficient nutritional strategies at lower costs. The research using mammary epithelial cells as a model elucidates metabolic changes under different nutrient availability conditions, offering insights into alternative pathways for milk protein synthesis.
Article
Cell Biology
Jessica Elswood, Scott J. Pearson, H. Ross Payne, Rola Barhoumi, Monique Rijnkels, Weston W. Porter
Summary: Through studying the differentiation and metabolism of mammary epithelial cells, it was found that mitophagy occurs selectively during the differentiation process. Inhibiting autophagy impairs cell differentiation, while the PRKN protein is necessary for cell differentiation.
Article
Endocrinology & Metabolism
Mathepan Jeya Mahendralingam, Hyeyeon Kim, Curtis William McCloskey, Kazeera Aliar, Alison Elisabeth Casey, Pirashaanthy Tharmapalan, Davide Pellacani, Vladimir Ignatchenko, Mar Garcia-Valero, Luis Palomero, Ankit Sinha, Jennifer Cruickshank, Ronak Shetty, Ravi N. Vellanki, Marianne Koritzinsky, Vid Stambolic, Mina Alam, Aaron David Schimmer, Hal Kenneth Berman, Connie J. Eaves, Miquel Angel Pujana, Thomas Kislinger, Rama Khokha
Summary: Cancer cells adapt their metabolic network from the tissue of origin. Normal mammary cells exhibit diverse metabolic programs, with basal cells enriched in glycolysis and luminal progenitors in oxidative phosphorylation. Targeting these metabolic vulnerabilities in mammary progenitors could potentially advance breast cancer therapy, as breast cancer subtypes retain metabolic features of their putative cell of origin.
Article
Agriculture, Dairy & Animal Science
Fang Wang, Jurgen van Baal, Lu Ma, Xuejun Gao, Jan Dijkstra, Dengpan Bu
Summary: This study investigated the role of MRCK alpha in milk protein and fat production in dairy cows and found a positive correlation between MRCK alpha expression and beta-casein levels in the mammary gland. Silencing MRCK alpha in bovine mammary epithelial cells led to a decrease in basal beta-casein and cell growth, while overexpression had the opposite effect. These findings suggest that MRCK alpha plays an important role in mammary tissue development.
Article
Cell Biology
Amritha Varshini Hanasoge Somasundara, Matthew A. Moss, Mary J. Feigman, Chen Chen, Samantha L. Cyrill, Michael F. Ciccone, Marygrace C. Trousdell, Macy Vollbrecht, Siran Li, Jude Kendall, Semir Beyaz, John E. Wilkinson, Camila O. dos Santos
Summary: Pregnancy induces expansion of NKT-like immune cells and upregulation of immune signaling molecules in mammary epithelial cells. Lack of CD1d expression or activated NKT cells may lead to mammary oncogenesis.
Article
Biochemistry & Molecular Biology
Rong Xuan, Jianmin Wang, Qing Li, Yanyan Wang, Shanfeng Du, Qingling Duan, Yanfei Guo, Peipei He, Zhibin Ji, Tianle Chao
Summary: This study conducted transcriptome sequencing of goat-mammary-gland tissue at different developmental stages to reveal the expression characteristics and molecular functions of circRNAs during mammary involution. A total of 11,756 circRNAs were identified, with 2528 circRNAs expressed in all three stages. Gene ontology analysis showed functional diversity of circRNAs' source genes. Furthermore, differentially expressed circRNAs and circRNA-miRNA-mRNA ceRNA regulatory networks were identified, providing insights into the regulatory role of circRNAs in mammary cell involution and remodeling.
Article
Oncology
Patricia Castillo, Omonigho Aisagoonhi, Cheryl C. Saenz, Wael M. ElShamy
Summary: Pregnancy-associated breast cancer (PABC) is a serious occurrence often of the triple negative (TNBC) subtype, which is diagnosed during or shortly after pregnancy. The expression of BRCA1-IRIS (IRIS) in human mammary epithelial cell lines can be upregulated by progesterone, prolactin, and RANKL, exacerbating cell proliferation, survival, and the TNBC-like phenotype. On the other hand, vitamin D-3 reduces IRIS expression in TNBC cell lines, attenuating cell growth, survival, and the TNBC-like phenotype.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Immunology
Sandy Haidar Ahmad, Sebastien Pasquereau, Ranim El Baba, Zeina Nehme, Clara Lewandowski, Georges Herbein
Summary: This study compared high-risk oncogenic HCMV-DB and BL strains with low-risk oncogenic strains HCMV-FS, KM, and SC, as well as the prototypic HCMV-TB40/E, showing that high-risk strains exhibit more pro-oncogenic features such as enhanced oncogene expression and mammosphere formation in vitro. The transcriptome of HMECs infected with HCMV clinical isolates displays an oncogenic gradient, with high-risk strains inducing a more prooncogenic environment that may contribute to breast cancer development.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Chi-Chin Sun, Shao-Yun Lee, Cheng-Heng Kao, Li-Hsien Chen, Zhao-Qing Shen, Chia-Hui Lai, Tsai-Yu Tzeng, Jong-Hwei Su Pang, Wen-Tai Chiu, Ting-Fen Tsai
Summary: The findings illustrate the crucial role of Cisd2 in the cornea and suggest that targeting the Ca2+ signaling pathway could be a potential therapeutic strategy for corneal epithelial diseases.
Article
Cell Biology
Taylor R. Rutherford, Alan M. Elder, Traci R. Lyons
Summary: The study reveals that SEMA7A promotes anoikis resistance in mammary epithelial cells and plays a role during mammary gland involution. SEMA7A is primarily expressed in cells expressing alpha 6-integrin, and a decrease in luminal progenitor cells is observed in SEMA7A-/- mice during involution.
CELL DEATH & DISEASE
(2021)
Article
Genetics & Heredity
Ambreen Iqbal, Pan Ziyi, Haibin Yu, Li Jialing, Wu Haochen, Fan Jing, Jiang Ping, Zhao Zhihui
Summary: The study reveals that C4BPA plays a role in regulating lipid metabolism through the PPAR signaling pathway and contributes to the inflammatory response through TLR-4/NF-kappa B and the complement and coagulation cascade pathways.
FRONTIERS IN GENETICS
(2022)
Article
Agriculture, Dairy & Animal Science
Yuhang Li, Qichao Hu, Zhuoma Luoreng, Jian Yang, Xingping Wang, Yun Ma, Dawei Wei
Summary: This study examined the role of miR-375 in bovine mammary epithelial cells (bMECs) and found that it potentially promotes inflammation in the mammary gland through the MAPK signaling pathway. The findings provide new insights into the regulation of bMEC inflammation and cow mastitis.
Article
Multidisciplinary Sciences
Patrick D. Radler, Barbara L. Wehde, Aleata A. Triplett, Hridaya Shrestha, Jonathan H. Shepherd, Adam D. Pfefferle, Hallgeir Rui, Robert D. Cardiff, Charles M. Perou, Kay-Uwe Wagner
Summary: Claudin-low breast cancer is an aggressive subtype mainly composed of triple-negative mammary tumor cells with stem cell-like and mesenchymal features. The consistent activation of oncogenic RAS signaling and regulators of EMT play crucial roles in maintaining the cellular plasticity and characteristics of claudin-low mammary cancer cells.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Christine Muttiah, James R. Whittle, Catherine Oakman, Geoffrey J. Lindeman
Summary: The current standard treatment for estrogen receptor-positive, HER2-negative metastatic breast cancer is endocrine therapy with a CDK4/6 inhibitor. This study aims to investigate the potential benefits of adding the BCL2 inhibitor venetoclax to the treatment regimen. A phase 1 trial will be conducted to determine the optimal dosages for combination therapy.
Article
Oncology
Luuk Heitink, James R. Whittle, Francois Vaillant, Bianca D. Capaldo, Johanna F. Dekkers, Caleb A. Dawson, Michael J. G. Milevskiy, Elliot Surgenor, Minhsuang Tsai, Huei-Rong Chen, Michael Christie, Yunshun Chen, Gordon K. Smyth, Marco J. Herold, Andreas Strasser, Geoffrey J. Lindeman, Jane E. Visvader
Summary: Breast cancer is a heterogeneous disease with multiple histological and molecular subtypes. This study describes a pipeline for identifying and validating tumor suppressor genes in breast cancer. Through in vivo and ex vivo experiments, several tumor suppressor genes were identified. The mutations in these genes were shown to accelerate tumor development in breast cancer.
MOLECULAR ONCOLOGY
(2022)
Article
Immunology
Yannick O. Alexandre, Dominik Schienstock, Hyun Jae Lee, Luke C. Gandolfo, Cameron G. Williams, Sapna Devi, Bhupinder Pal, Joanna R. Groom, Wang Cao, Susan N. Christo, Claire L. Gordon, Graham Starkey, Rohit D'Costa, Laura K. Mackay, Ashraful Haque, Burkhard Ludewig, Gabrielle T. Belz, Scott N. Mueller
Summary: This article provides a comprehensive understanding of the cellular and molecular characteristics of fibroblastic stromal cells in the spleen, revealing their significance and diversity in maintaining tissue homeostasis and orchestrating immune responses.
SCIENCE IMMUNOLOGY
(2022)
Article
Oncology
Geoffrey J. Lindeman, Tharu M. Fernando, Rebecca Bowen, Katarzyna J. Jerzak, Xinni Song, Thomas Decker, Frances Boyle, Steve McCune, Anne Armstrong, Catherine Shannon, Gianfilippo Bertelli, Ching-Wei Chang, Rupal Desai, Kushagra Gupta, Timothy R. Wilson, Aulde Flechais, Aditya Bardia
Summary: The combination of venetoclax and fulvestrant did not show clinical utility in endocrine therapy-resistant, CDK4/6 inhibitor-refractory metastatic breast cancer, but suggested a possible increased dependence on BCLXL in this setting.
CLINICAL CANCER RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Ravian L. van Ineveld, Esmee J. van Vliet, Ellen J. Wehrens, Maria Alieva, Anne C. Rios
Summary: This article introduces the importance and potential applications of 3D imaging in cancer research. 3D imaging provides more accurate information about the cellular composition and structure of cancer, and offers new strategies and methods for cancer treatment and patient diagnosis.
Article
Multidisciplinary Sciences
Yunshun Chen, Bhupinder Pal, Geoffrey J. Lindeman, Jane E. Visvader, Gordon K. Smyth
Summary: This article extends our understanding of the development mechanism of breast cancer by providing quality control thresholds, processed data objects, complete cell annotation, and R code for analysis of a large-scale single-cell RNA expression atlas.
Article
Hematology
Charis E. Teh, Hongke Peng, Meng-Xiao Luo, Tania Tan, Marie Trussart, Lauren J. Howson, Chong Chyn Chua, Christine Muttiah, Fiona Brown, Matthew E. Ritchie, Andrew H. Wei, Andrew W. Roberts, Vanessa L. Bryant, Mary Ann Anderson, Geoffrey J. Lindeman, David C. S. Huang, Rachel Thijssen, Daniel H. D. Gray
Summary: Venetoclax is effective for certain blood cancers, but relapse is common. Combining it with immunotherapies is promising, but its impact on normal immune cells is unclear. This study found minimal impact on T and NK cells, supporting the potential combination of Venetoclax with immunotherapies for better anti-tumor responses.
Review
Biochemistry & Molecular Biology
Emma Nolan, Geoffrey J. Lindeman, Jane E. Visvader
Summary: Breast cancer is a major cause of cancer-related death in women due to its heterogeneity, metastasis, and resistance to treatment. Recent advances in genomics and transcriptomics have revealed distinct subtypes, molecular drivers, evolutionary patterns, and prognostic markers. Moreover, the integration of high-resolution single-cell and spatial technologies has revealed the significance of the breast cancer ecosystem and different cellular neighborhoods.
Article
Medicine, General & Internal
Dilanka L. De Silva, Lesley Stafford, Anita R. Skandarajah, Michelle Sinclair, Lisa Devereux, Kirsten Hogg, Maira Kentwell, Allan Park, Luxi Lal, Magnus Zethoven, Madawa W. Jayawardana, Fiona Chan, Phyllis N. Butow, Paul A. James, G. Bruce Mann, Ian G. Campbell, Geoffrey J. Lindeman
Summary: This study aimed to assess the feasibility of universal genetic testing for women with newly diagnosed breast cancer. The study found that 6.5% of participants had pathogenic germline variants, and 18 of them did not meet the current genetic testing eligibility guidelines. Clinical management was changed for 24 women after the identification of pathogenic variants. Acceptance of universal testing was high among both patients and clinicians.
MEDICAL JOURNAL OF AUSTRALIA
(2023)
Article
Multidisciplinary Sciences
Jeff DeMartino, Michael T. Meister, Lindy L. Visser, Mariel Brok, Marian J. A. Groot Koerkamp, Amber K. L. Wezenaar, Laura S. Hiemcke-Jiwa, Terezinha de Souza, Johannes H. M. Merks, Anne C. Rios, Frank C. P. Holstege, Thanasis Margaritis, Jarno Drost
Summary: This study explores the cellular differentiation states of paediatric rhabdomyosarcoma (RMS) using single-cell RNA sequencing analysis and identifies an immunosuppressive microenvironment and transcriptional programs predictive of patient outcomes. The research generates a transcriptomic atlas of RMS and reveals evidence of an immunosuppressive microenvironment in the RMS tumour niche. The study also highlights the potential of therapies targeting the immune microenvironment and suggests that assessing tumour differentiation states may enable a more refined risk stratification.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Michael J. G. Milevskiy, Hannah D. Coughlan, Serena R. Kane, Timothy M. Johanson, Somayeh Kordafshari, Wing Fuk Chan, Minhsuang Tsai, Elliot Surgenor, Stephen Wilcox, Rhys S. Allan, Yunshun Chen, Geoffrey J. Lindeman, Gordon K. Smyth, Jane E. Visvader
Summary: This study provides a comprehensive analysis of the chromatin landscape of epithelial subsets in the mammary gland, revealing the contribution of 3D genome organization to gene regulation in the epithelium. The results demonstrate that lineage-specific genes exhibit lineage specificity through distal enhancers, while luminal-specific genes display promoter priming in basal cells. Chromatin interactions with super enhancers and polycomb silencer elements play a major role in the cell specificity of luminal progenitors.
Article
Biochemistry & Molecular Biology
Shikhar Sharma, Chi-Yeh Chung, Sean Uryu, Jelena Petrovic, Joan Cao, Amanda Rickard, Nataliya Nady, Samantha Greasley, Eric Johnson, Oleg Brodsky, Showkhin Khan, Hui Wang, Zhenxiong Wang, Yong Zhang, Konstantinos Tsaparikos, Lei Chen, Anthony Mazurek, John Lapek, Pei-Pei Kung, Scott Sutton, Paul F. Richardson, Eric C. Greenwald, Shinji Yamazaki, Rhys Jones, Karen A. Maegley, Patrick Bingham, Hieu Lam, Alexandra E. Stupple, Aileen Kamal, Anderly Chueh, Anthony Cuzzupe, Benjamin J. Morrow, Bin Ren, Catalina Carrasco-Pozo, Chin Wee Tan, Dharmesh D. Bhuva, Elizabeth Allan, Elliot Surgenor, Francois Vaillant, Havva Pehlivanoglu, Hendrik Falk, James R. Whittle, Janet Newman, Joseph Cursons, Judy P. Doherty, Karen L. White, Laura Macpherson, Mark Devlin, Matthew L. Dennis, Meghan K. Hattarki, Melanie De Silva, Michelle A. Camerino, Miriam S. Butler, Olan Dolezal, Patricia Pilling, Richard Foitzik, Paul A. Stupple, H. Rachel Lagiakos, Scott R. Walker, Soroor Hediyeh-Zadeh, Stewart Nuttall, Sukhdeep Spall, Susan A. Charman, Theresa Connor, Thomas S. Peat, Vicky M. Avery, Ylva E. Bozikis, Yuqing Yang, Ming Zhang, Brendon J. Monahan, Anne K. Voss, Ian P. Street, Sarah-Jane Dawson, Mark A. Dawson, Geoffrey J. Lindeman, Melissa J. Davis, Jane E. Visvader, Thomas A. Paul
Summary: In this study, a highly potent, selective, and orally bioavailable KAT6A/KAT6B inhibitor CTx-648 was identified, which inhibits H3K23 acetylation and exhibits anti-tumor activity in ER+ breast cancer. The mechanism of action may involve the modulation of transcriptional and epigenetic profiles.
CELL CHEMICAL BIOLOGY
(2023)
Review
Oncology
Maria Alieva, Amber K. L. Wezenaar, Ellen J. Wehrens, Anne C. Rios
Summary: Live-cell imaging provides a deeper understanding of cancer response to treatment by offering spatial, molecular, and morphological data over time. It has been applied to uncover tumour heterogeneity in treatment response and the mode of action of cancer-targeting drugs. The unique opportunity of time-lapse imaging in capturing the interactivity and motility of immunotherapies is also discussed. Recent technological advancements in multidimensional imaging and multi-omics data integration have allowed for the connection of single-cell dynamics to molecular phenotypes. These advancements significantly contribute to our understanding of tumour targeting and have implications for next-generation precision medicine.
NATURE REVIEWS CANCER
(2023)
Article
Oncology
Thomas U. Ahearn, Haoyu Zhang, Kyriaki Michailidou, Roger L. Milne, Manjeet K. Bolla, Joe Dennis, Alison M. Dunning, Michael Lush, Qin Wang, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Kristan J. Aronson, Paul L. Auer, Annelie Augustinsson, Adinda Baten, Heiko Becher, Sabine Behrens, Javier Benitez, Marina Bermisheva, Carl Blomqvist, Stig E. Bojesen, Bernardo Bonanni, Anne-Lise Borresen-Dale, Hiltrud Brauch, Hermann Brenner, Angela Brooks-Wilson, Thomas Bruening, Barbara Burwinkel, Saundra S. Buys, Federico Canzian, Jose E. Castelao, Jenny Chang-Claude, Stephen J. Chanock, Georgia Chenevix-Trench, Christine L. Clarke, J. Margriet Collee, Angela Cox, Simon S. Cross, Kamila Czene, Mary B. Daly, Peter Devilee, Thilo Dork, Miriam Dwek, Diana M. Eccles, D. Gareth Evans, Peter A. Fasching, Jonine Figueroa, Giuseppe Floris, Manuela Gago-Dominguez, Susan M. Gapstur, Jose A. Garcia-Saenz, Mia M. Gaudet, Graham G. Giles, Mark S. Goldberg, Anna Gonzalez-Neira, Grethe I. Grenaker Alnaes, Mervi Grip, Pascal Guenel, Christopher A. Haiman, Per Hall, Ute Hamann, Elaine F. Harkness, Bernadette A. M. Heemskerk-Gerritsen, Bernd Holleczek, Antoinette Hollestelle, Maartje J. Hooning, Robert N. Hoover, John L. Hopper, Anthony Howell, Milena Jakimovska, Anna Jakubowska, Esther M. John, Michael E. Jones, Audrey Jung, Rudolf Kaaks, Saila Kauppila, Renske Keeman, Elza Khusnutdinova, Cari M. Kitahara, Yon-Dschun Ko, Stella Koutros, Vessela N. Kristensen, Ute Kruger, Katerina Kubelka-Sabit, Allison W. Kurian, Kyriacos Kyriacou, Diether Lambrechts, Derrick G. Lee, Annika Lindblom, Martha Linet, Jolanta Lissowska, Ana Llaneza, Wing-Yee Lo, Robert J. MacInnis, Arto Mannermaa, Mehdi Manoochehri, Sara Margolin, Maria Elena Martinez, Catriona McLean, Alfons Meindl, Usha Menon, Heli Nevanlinna, William G. Newman, Jesse Nodora, Kenneth Offit, Hakan Olsson, Nick Orr, Tjoung-Won Park-Simon, Alpa Patel, Julian Peto, Guillermo Pita, Dijana Plaseska-Karanfilska, Ross Prentice, Kevin Punie, Katri Pylkas, Paolo Radice, Gad Rennert, Atocha Romero, Thomas Ruediger, Emmanouil Saloustros, Sarah Sampson, Dale P. Sandler, Elinor J. Sawyer, Rita K. Schmutzler, Minouk J. Schoemaker, Ben Schottker, Mark E. Sherman, Xiao-Ou Shu, Snezhana Smichkoska, Melissa C. Southey, John J. Spinelli, Anthony J. Swerdlow, Rulla M. Tamimi, William J. Tapper, Jack A. Taylor, Lauren R. Teras, Mary Beth Terry, Diana Torres, Melissa A. Troester, Celine M. Vachon, Carolien H. M. van Deurzen, Elke M. van Veen, Philippe Wagner, Clarice R. Weinberg, Camilla Wendt, Jelle Wesseling, Robert Winqvist, Alicja Wolk, Xiaohong R. Yang, Wei Zheng, Fergus J. Couch, Jacques Simard, Peter Kraft, Douglas F. Easton, Paul D. P. Pharoah, Marjanka K. Schmidt, Montserrat Garcia-Closas, Nilanjan Chatterjee
Summary: This study identifies breast cancer susceptibility variants that are associated with tumor features and intrinsic molecular subtypes, providing insights for subtype-specific risk prediction.
BREAST CANCER RESEARCH
(2022)