Article
Pharmacology & Pharmacy
Thiago S. Lima, Luciano O. Souza, Diego Iglesias-Gato, Johanna Elversang, Flemming Steen Jorgensen, Tuula Kallunki, Martin A. Roder, Klaus Brasso, Jose M. A. Moreira
Summary: Itraconazole can re-sensitize docetaxel-resistant prostate and breast cancer cells by binding to ABC transporter protein ABCB1, inhibiting the transport of docetaxel.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Cara Van Der Wal, Shane T. Ahyong, Maxim W. D. Adams, Kyle M. Ewart, Simon Y. W. Ho, Nathan Lo
Summary: Australia is a center of diversity for freshwater crayfish, particularly in the genus Euastacus. The genetic diversity and population structure of Euastacus spinifer were investigated, revealing a species complex with a close relative E. vesper. The results also suggest isolated and fragmented populations of a previously widespread ancestral species, raising the number of species within the E. spinifer complex to at least three. This study highlights the threats faced by freshwater crayfish due to their restricted and fragmented distributions, contributing to their endangered status globally.
MOLECULAR PHYLOGENETICS AND EVOLUTION
(2023)
Article
Multidisciplinary Sciences
Meiou Dai, Gang Yan, Ni Wang, Girija Daliah, Ashlin M. Edick, Sophie Poulet, Julien Boudreault, Suhad Ali, Sergio A. Burgos, Jean-Jacques Lebrun
Summary: Through in vivo genome-wide CRISPR screening, tumor regulatory functions for components of the mTORC1/2 complex and YAP/Hippo pathway were identified in TNBC, showing that pharmacological inhibition of mTOR and YAP can reduce tumor growth in vivo.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Megan Crow, Hamsini Suresh, John Lee, Jesse Gillis
Summary: Differences in gene regulation play a critical role in cell specialization and diversification, and the differential regulation of ancient gene programs contributes to transcriptional cell identity.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cell Biology
Sean W. Minaker, Megan C. Kofoed, Philip Hieter, Peter C. Stirling
Summary: The study elucidates the specificity of GPN2 for RNA polymerases by screening the localization of GFP-tagged nuclear proteins, highlighting the significant impact of GPN2 on RNA polymerase II and III subunits. It also uncovers a previously underappreciated role of CTD modification in RNAPII nuclear localization.
Article
Cell Biology
Yan-Xiao Ji, Yutao Wang, Peng-Long Li, Lin Cai, Xiao-Ming Wang, Lan Bai, Zhen Liu, Han Tian, Song Tian, Peng Zhang, Xiao-Jing Zhang, Xu Cheng, Yufeng Yuan, Zhi-Gang She, Yufeng Hu, Hongliang Li
Summary: The study identified Nemo-like kinase (NLK) as a potent suppressor of excessive hepatic glucose production, which is a major cause of fasting hyperglycemia. Restoring NLK expression in diabetic rodent models ameliorated hyperglycemia, suggesting NLK as a potential therapeutic target for T2D.
Article
Microbiology
Yu Wang, Han Fu, Xiao-Jie Shi, Guo-Ping Zhao, Liang-Dong Lyu
Summary: The antibacterial activity of rifamycins relies on the inhibition of transcription by directly binding to bacterial DNA-dependent RNA polymerase (RNAP). However, this killing efficacy is limited in most gram-negative bacteria. In this study, we identified the cellular functions that counteract rifamycin-mediated killing in Escherichia coli, a gram-negative model organism, and found that the beta-barrel assembly machinery plays a crucial role in restricting rifampicin from entering the cell. Additionally, cellular functions such as iron acquisition, DNA repair, aerobic respiration, and carbon metabolism strongly influenced the killing efficacy of rifampicin. Maintenance of DNA replication and transcription-coupled nucleotide excision repair protected E. coli cells against rifampicin killing, while sustained aerobic respiration and carbon catabolism diminished rifampicin's killing efficacy.
MICROBIOLOGY SPECTRUM
(2023)
Article
Cell & Tissue Engineering
Francesca Rapino, Ted Natoli, Francesco Limone, Erin O'Connor, Jack Blank, Matthew Tegtmeyer, William Chen, Erika Norabuena, Juhi Narula, Dane Hazelbaker, Gabriella Angelini, Lindy Barrett, Alison O'Neil, Ursula K. Beattie, Jessica M. Thanos, Heather de Rivera, Steven D. Sheridan, Roy H. Perlis, Steven A. McCarroll, Beth Stevens, Aravind Subramanian, Ralda Nehme, Lee L. Rubin
Summary: In the brain, the complement system is important in the immune response and synaptic elimination. This study identified pathways that regulate the production of complement component 4 (C4), linked to increased schizophrenia risk. A 3D protocol was developed to produce astrocytes, and a small-molecule screen identified regulators of C4 secretion. Additional regulatory pathways were predicted and validated, including one involving c-Jun-kinase. This research lays the foundation for developing therapies targeting the complement cascade in CNS diseases.
Article
Oncology
Alana Sorgini, Hugh Andrew Jinwook Kim, Peter Y. F. Zeng, Mushfiq Hassan Shaikh, Neil Mundi, Farhad Ghasemi, Eric Di Gravio, Halema Khan, Danielle MacNeil, Mohammed Imran Khan, Adrian Mendez, John Yoo, Kevin Fung, Pencilla Lang, David A. Palma, Joe S. Mymryk, John W. Barrett, Krupal B. Patel, Paul C. Boutros, Anthony C. Nichols
Summary: Squamous cell carcinomas from different subsites of the larynx display distinct molecular profiles, including differences in genome mutations, enriched protein pathways, and differential protein abundance. These differences may partially account for variations in prognosis and response to therapy between cancers from different subsites.
Article
Oncology
Yu Yu, Minzhen Tao, Libin Xu, Lei Cao, Baoyu Le, Na An, Jilin Dong, Yajie Xu, Baoxing Yang, Wei Li, Bing Liu, Qiong Wu, Yinying Lu, Zhen Xie, Xiaohua Lian
Summary: Pair-wise sgRNA library screening provided systematic insights into elucidating MAPKi resistance in cancer cells. Targeting drugs (cilengitide + linsitinib) could be used as an effective therapy for suppressing the adaptive formation of the HDGF-LGR5 protein complex, which enhanced cancer stemness during MAPKi stress.
CANCER BIOLOGY & MEDICINE
(2022)
Article
Zoology
Chun-Long Yan, Jun Lin, Yuan-Yuan Huang, Qing-Shan Gao, Zheng-Yu Piao, Shou-Li Yuan, Li Chen, Xue Ren, Rong-Cai Ye, Meng Dong, Han-Lin Zhang, Hui-Qiao Zhou, Xiao-Xiao Jiang, Wan-Zhu Jin, Xu-Ming Zhou, Chang-Guo Yan
Summary: Environmental temperature plays a significant role in shaping genetic variation in domestic cattle, with the PRDM16 gene identified as crucial in maintaining brown adipocyte formation in northern cattle for cold tolerance.
ZOOLOGICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Sabine Pinter, Franziska Knodel, Michel Choudalakis, Philipp Schnee, Carolin Kroll, Marina Fuchs, Alexander Broehm, Sara Weirich, Mareike Roth, Stephan A. Eisler, Johannes Zuber, Albert Jeltsch, Philipp Rathert
Summary: In this study, we identified DEAD-box helicase 19A (DDX19A) as a novel coregulator of lysine specific demethylase 1 (LSD1), which regulates gene expression by controlling the trimethylation of lysine 27 on histone 3. This discovery sheds light on a novel transcriptional regulatory pathway involving LSD1, DDX19A, and histone modifications.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biology
Abderrahman Hachani, Stefano G. Giulieri, Romain Guerillot, Calum J. Walsh, Marion Herisse, Ye Mon Soe, Sarah L. Baines, David R. Thomas, Shane Doris Cheung, Ashleigh S. Hayes, Ellie Cho, Hayley J. Newton, Sacha Pidot, Ruth C. Massey, Benjamin P. Howden, Timothy P. Stinear
Summary: This study developed the InToxSa platform to quantify intracellular cytotoxic Staphylococcus aureus phenotypes and discovered clinically relevant mutations that reduce bacterial cytotoxicity and promote intracellular persistence.
Article
Biotechnology & Applied Microbiology
Xiaowei Peng, Wenying Zhang, Chengfeng Lei, Shuifa Min, Jia Hu, Qinghua Wang, Xiulian Sun
Summary: This study compared two Chinese isolates of Hyphantria cunea nucleopolyhedrovirus with a Japanese isolate to determine their genetic diversity. The results showed that the Chinese isolates belonged to a novel species of Alphabaculovirus and exhibited significant differences in gene contents, including gene deletions, acquisitions, and structural transversions. The study also found a high number of single nucleotide polymorphisms (SNPs) in the Chinese isolates. Biological activity assays showed variations in infectivity and killing speed between the two Chinese isolates. The differences in virulence were attributed to SNPs and structural variants, particularly in the homologous repeat regions.
Article
Plant Sciences
Shi-Hao Ni, Xiao-Lu OuYang, Xin Liu, Jin-Hai Lin, Yue Li, Shu-Ning Sun, Jian-Ping Deng, Xiao-Wei Han, Xiao-Jiao Zhang, Huan Li, Yu-Sheng Huang, Zi-Xin Chen, Zhi-Ming Lian, Zhen-Kui Wang, Wen-Jie Long, Ling-Jun Wang, Zhong-Qi Yang, Lu Lu
Summary: This study identifies LBT as a potential treatment for cardiorenal syndrome type 4 (CRS) by inhibiting OPN expression through the JNK pathway. The findings provide new insights into CRS drug discovery.
Article
Multidisciplinary Sciences
Marisa Nacke, Emma Sandilands, Konstantina Nikolatou, Alvaro Roman-Fernandez, Susan Mason, Rachana Patel, Sergio Lilla, Tamas Yelland, Laura C. A. Galbraith, Eva C. Freckmann, Lynn McGarry, Jennifer P. Morton, Emma Shanks, Hing Y. Leung, Elke Markert, Shehab Ismail, Sara Zanivan, Karen Blyth, David M. Bryant
Summary: The study reveals that different isoforms of the ARF GTPase exchange factor IQSEC1 direct phosphoinositide metabolism to promote invasive responses in cells rather than growth responses.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Mate Naszai, Karen Bellec, Yachuan Yu, Alvaro Roman-Fernandez, Emma Sandilands, Joel Johansson, Andrew D. Campbell, Jim C. Norman, Owen J. Sansom, David M. Bryant, Julia B. Cordero
Summary: RAL GTPases activate EGFR/MAPK signaling in the intestine, impacting stem cell proliferation and tumorigenic growth, revealing their essential role in adult tissue homeostasis and malignant transformation.
Article
Cell Biology
Robert G. Bristow, Joanne Engel, Izzy Jayasinghe, Martin Kampmann, Owen James Sansom, David M. Bryant
Summary: This article introduces LGBT+ History Month in February, and describes a conversation organized by David Bryant, a member of the Journal of Cell Science Editorial Advisory Board, with a group of scientists to discuss their experiences as LGBT+ individuals in academia.
JOURNAL OF CELL SCIENCE
(2022)
Article
Oncology
Fortis Gaba, William J. Tipping, Mark Salji, Karen Faulds, Duncan Graham, Hing Y. Leung
Summary: Raman spectroscopic analysis is a promising optical tool for detecting molecular composition in prostate cancer. It is non-destructive, non-invasive, and allows for real-time evaluation of treatment efficacy. Raman techniques can be applied in biopsy analysis, assessment of surgical margins, and treatment monitoring.
Article
Multidisciplinary Sciences
Eva C. Freckmann, Emma Sandilands, Erin Cumming, Matthew Neilson, Alvaro Roman-Fernandez, Konstantina Nikolatou, Marisa Nacke, Tamsin R. M. Lannagan, Ann Hedley, David Strachan, Mark Salji, Jennifer P. Morton, Lynn McGarry, Hing Y. Leung, Owen J. Sansom, Crispin J. Miller, David M. Bryant
Summary: Currently, there is a lack of tools to detect heterogeneity in 3D cultures. This study introduces Traject3d as a framework to identify and understand heterogeneous states in 3D culture and their impact on distinct phenotypes. The findings provide valuable insights into the temporal landscape of morphological states and drug combinations that inhibit heterogeneity.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Alvaro Roman-Fernandez, Mohammed A. Mansour, Fernanda G. Kugeratski, Jayanthi Anand, Emma Sandilands, Laura Galbraith, Kai Rakovic, Eva C. Freckmann, Erin M. Cumming, Ji Park, Konstantina Nikolatou, Sergio Lilla, Robin Shaw, David Strachan, Susan Mason, Rachana Patel, Lynn McGarry, Archana Katoch, Kirsteen J. Campbell, Colin Nixon, Crispin J. Miller, Hing Y. Leung, John Le Quesne, James C. Norman, Sara Zanivan, Karen Blyth, David M. Bryant
Summary: PODXL is important for tissue development by promoting apical membranes and lumen formation. However, elevated PODXL expression is associated with metastasis and poor clinical outcome in tumors. We unexpectedly found that PODXL acts as a decoy receptor for GAL3, releasing GAL3 repression of integrin-based invasion. Differential cortical targeting of PODXL, regulated by ubiquitination, determines its alternate functions. Both high and low surface levels of PODXL exist in cancer cells, and this axis controls metastasis in vivo. The interaction between PODXL and GAL3 can stratify prostate cancer patients with poor outcome.
Article
Oncology
Amy J. Tibbo, Andrew Hartley, Richa Vasan, Robin Shaw, Laura Galbraith, Ernest Mui, Hing Y. Leung, Imran Ahmad
Summary: The study found that the MBTPS2 gene alteration is associated with metastatic prostate cancer, and it is involved in the development of prostate cancer through its regulation of fatty acid and cholesterol metabolism.
BRITISH JOURNAL OF CANCER
(2023)
Article
Cell Biology
Emma Sandilands, Eva C. Freckmann, Erin M. Cumming, Alvaro Roman-Fernandez, Lynn McGarry, Jayanthi Anand, Laura Galbraith, Susan Mason, Rachana Patel, Colin Nixon, Jared Cartwright, Hing Y. Leung, Karen Blyth, David M. Bryant
Summary: Sandilands et al. discovered that ARF3 plays a role in regulating invasion and metastasis in prostate cancer patients by controlling the turnover of N-cadherin. ARF GTPases are essential for membrane trafficking and vesicle formation. ARF3 acts as a switch between leader cell-led chains of invasion or collective sheet movement by controlling the modality of invasion.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Medicine, General & Internal
Maha AlRasheedi, Sai Han, Helene Thygesen, Matt Neilson, Fraser Hendry, Ahmed Alkarn, John D. D. Maclay, Hing Y. Y. Leung
Summary: F-18-FDG positron emission tomography with computed tomography (PET/CT) is the standard imaging modality for nodal staging in non-small cell lung cancer (NSCLC). To improve pre-operative staging accuracy, the study compares the staging accuracy of standardized uptake values (SUV) of mediastinal lymph nodes with four derived SUV ratios. The results show that normalized SUV ratios, especially liver SUV, improve current pre-operative staging performance in detecting mediastinal nodal involvement.
Review
Biochemistry & Molecular Biology
Konstantina Nikolatou, David M. Bryant, Emma Sandilands
Summary: The ability to polarize cellular membranes and coordinate this polarization between cells is essential for specialized functions in different regions of the cell, and dysregulation of tissue polarization can drive metastasis during tumorigenesis. This review focuses on how membrane trafficking, specifically controlled by the ADP-ribosylation factor (ARF) subfamily of small GTPases, underlies collective cell invasion and metastasis in cancer.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Konstantina Nikolatou, Emma Sandilands, Alvaro Roman-Fernandez, Erin M. Cumming, Eva Freckmann, Sergio Lilla, Lori Buetow, Lynn McGarry, Matthew Neilson, Robin Shaw, David Strachan, Crispin Miller, Danny T. Huang, Iain A. McNeish, James C. Norman, Sara Zanivan, David M. Bryant
Summary: Dysregulation of the PI3K/AKT pathway is common in HGSOC, and loss of the tumor suppressor PTEN is associated with poor prognosis. The mechanisms of PTEN loss in HGSOC are largely unknown. In this study, time-lapse imaging and machine learning were used to classify the phenotype of PTEN loss in HGSOC spheroids. PTEN deficiency induced membrane protrusions into the extracellular matrix, leading to a collective invasion phenotype. The small GTPase ARF6 was identified as a vulnerability in HGSOC cells with PTEN loss.