Article
Cell Biology
Victoria Gudino, Patrizia Cammareri, Caroline Billard, Kevin B. Myant
Summary: RAC1B, overexpressed in tumors, may not necessarily drive tumor invasion but accelerate tumor initiation with reduced apoptosis. It functions by attenuating TGF beta signaling and conferring resistance to TGF beta-driven cell death in early-stage adenoma cells. This study reveals a novel oncogenic function of RAC1B in vivo.
CELL DEATH & DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Yanan Li, Sara Giovannini, Tingting Wang, Jiankai Fang, Peishan Li, Changshun Shao, Ying Wang, Yufang TOR Ctr, Yufang Shi, Eleonora Candi, Gerry Melino, Francesca Bernassola
Summary: Epithelial tissue homeostasis is closely associated with the self-renewal and differentiation behaviors of epithelial stem cells (ESCs). p63, a well-known marker of ESCs, regulates the transcription of genes involved in cell survival, stem cell self-renewal, migration, differentiation, and epithelial-to-mesenchymal transition. p63 plays a crucial role in normal epithelial development and epithelium-derived cancer pathogenesis.
Article
Environmental Sciences
Jingxuan Wang, Yan Hu, Jieying Yuan, Yan Zhang, Yifan Wang, Yingshun Yang, Tahani Awad Alahmadi, Sulaiman Ali Alharbi, Zhizheng Zhuang, Fan Wu
Summary: The study found that Neferine has a protective effect against oral carcinoma, delaying lesion synthesis and restoring biochemical parameters in hamsters. Neferine inhibits NF-kB, PCNA, and p53 through immunostaining, suggesting its potential as a chemopreventive drug in experimental models of oral carcinomas. More research is needed to explore other pathways involved in oral carcinomas and their modulation by Neferine.
ENVIRONMENTAL TOXICOLOGY
(2021)
Article
Medicine, Research & Experimental
Tongshuai Chen, Chang Ma, Guanqi Fan, Hui Liu, Xie Lin, Jingyuan Li, Na Li, Shujian Wang, Mei Zeng, Yun Zhang, Peili Bu
Summary: Hyperglycemia accelerates endothelial cell dysfunction and vascular complications by inducing ECs senescence, with molecular mechanisms involving SIRT3-p53 pathway.
Article
Biochemistry & Molecular Biology
Young Yeon Kim, Jee-Hyun Um, Dong Jin Shin, Dae Jin Jeong, Young Bin Hong, Jeanho Yun
Summary: The tumor suppressor p53 regulates mitochondrial dynamics through the PKA-Drp1 pathway, inducing cellular senescence in various cancer and normal cells. It plays an essential role in H-Ras-induced cellular senescence and replicative senescence in normal human cells. Inhibition of PKA activity reduces mitochondrial elongation and cellular senescence in late-passage normal cells, highlighting the importance of the p53-PKA pathway in maintaining the senescence phenotype.
Article
Medicine, Research & Experimental
Seda Beyaz, Abdullah Aslan, Ozlem Gok, Harun Uslu, Can Ali Agca, Ibrahim Hanifi Ozercan
Summary: The study demonstrates the protective and therapeutic effect of fullerene C-60 nanoparticles on DMBA-induced breast cancer in rats. In vitro experiments show that fullerene C-60 inhibits the viability of MCF-7 cells. In vivo experiments reveal changes in apoptotic and inflammatory protein levels in rats treated with fullerene C-60.
Article
Multidisciplinary Sciences
Kenji Tago, Satoshi Ohta, Chihiro Aoki-Ohmura, Megumi Funakoshi-Tago, Miho Sashikawa, Takeshi Matsui, Yuki Miyamoto, Taeko Wada, Tomoyuki Oshio, Mayumi Komine, Jitsuhiro Matsugi, Yusuke Furukawa, Mamitaro Ohtsuki, Junji Yamauchi, Ken Yanagisawa
Summary: NKIRAS1 and NKIRAS2 were identified as atypical RAS family members that may act as tumor suppressors in some contexts, but as necessary factors in oncogenic transformation in other situations. The expression levels of NKIRAS likely determine its functional role in carcinogenesis.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, Research & Experimental
Deepak Hiraganahalli Bhaskarmurthy, Sabina Evan Prince
Summary: In this study, topical application of Baricitinib showed promising therapeutic effects on chronic TPA-induced psoriasis in mice, effectively inhibiting inflammation and promoting skin repair. Baricitinib significantly reduced ear swelling, leukocyte infiltration, cell proliferation, and angiogenesis, while also decreasing the phosphorylation of STAT3 and STAT1. These results suggest that Baricitinib could be a potential topical treatment for the progression of psoriasis.
Review
Oncology
Anindita Chakrabarty, Shayantani Chakraborty, Ranjini Bhattacharya, Goutam Chowdhury
Summary: This paper focuses on chemotherapy resistance in triple negative breast cancer (TNBC) due to therapy-induced senescence (TIS). Senescent cells and the senescence-associated secretory proteome (SASP) play a role in promoting drug resistance and aggressive clones in cancer. Strategies to control TIS using evolutionary biology principles are proposed to improve therapeutic outcomes for TNBC patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Bing Si Li, Ai Lin Jin, ZiQi Zhou, Jae Ho Seo, Byung-Min Choi
Summary: The study showed that DRG2 is upregulated in oxidative stress-induced premature senescence and aged tissues, promoting cellular aging through multiple pathways such as inhibiting SIRT1, increasing acetylation of p53 and NF-kappa B p65, and elevating ROS and γ-H2A.X levels.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2021)
Article
Cell Biology
Tapasi Rana, Chunsun Jiang, Sami Banerjee, Nengjun Yi, Jaroslaw W. Zmijewski, Gang Liu, Rui-Ming Liu
Summary: Cellular senescence, especially the senescence of alveolar epithelial type II (ATII) cells, plays a crucial role in aging and aging-related diseases such as idiopathic pulmonary fibrosis (IPF). Plasminogen activator inhibitor 1 (PAI-1), a serine protease inhibitor, was found to bind to proteasome components and inhibit proteasome activity, leading to ATII cell senescence by preventing p53 degradation. This study provides insights into the molecular mechanisms underlying ATII cell senescence and its potential implications for the pathogenesis of lung fibrosis and other age-related diseases.
Article
Biochemistry & Molecular Biology
Hao Yang, Ke Zhang, Yusheng Guo, Xin Guo, Kailong Hou, Jing Hou, Ying Luo, Jing Liu, Shuting Jia
Summary: One of the critical steps in tumorigenic transformation is bypassing senescence. This study investigated the role of the p53S mutation in senescence bypass and found that it increased the level and nuclear translocation of PGC-1 alpha, promoting mitochondrial biosynthesis and function. Additionally, p53S regulated the interaction between PGC-1 alpha and PPAR gamma, promoting lipid synthesis as a potential pathway for escaping aging.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Wei Zhao, Huanye Mo, Runkun Liu, Tianxiang Chen, Nan Yang, Zhikui Liu
Summary: KAT6A is upregulated in hepatocellular carcinoma (HCC) tissues and cell lines and is associated with malignant prognostic features and shorter survival. It acetylates lysine 23 of histone H3 (H3K23), enhances the association between the nuclear receptor binding protein TRIM24 and H3K23ac, and activates the transcription and expression of SOX2, leading to HCC tumorigenesis.
BRITISH JOURNAL OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Jingkun Zeng, Stephanie A. Hills, Eiko Ozono, John F. X. Diffley
Summary: Whole-genome duplication (WGD) is a frequent event in cancer evolution, and the p53 tumor suppressor plays a dual role in this process. It can act as a barrier to WGD by blocking the proliferation of tetraploid cells, but it can also promote mitotic bypass, a key step in WGD. In wild-type p53 tumors, WGD is often associated with activation of the E2F pathway, particularly the amplification of CCNE1. High expression of cyclin E1 causes replicative stress, leading to G2 phase arrest. p53, along with its downstream target p21 and Wee1, inhibits mitotic cyclin-dependent kinase activity, activating APC/CCdh1 and promoting mitotic bypass.
Article
Chemistry, Medicinal
Jie Wang, Zhenxing He, Juhua Zhao, Wenming Xiao, Lingling Xiong, Wei Chen
Summary: The study found that brucine has anticancer effects on DMBA-induced skin cancer in a mouse model by suppressing cell proliferation and inducing apoptosis through regulating the PI3K/AKT signaling pathway.
PHARMACOGNOSY MAGAZINE
(2022)
Article
Genetics & Heredity
Lin Xu, Tingjian Zu, Tao Li, Min Li, Jun Mi, Fuxiang Bai, Guanyi Liu, Jie Wen, Hui Li, Cord Brakebusch, Xuxia Wang, Xunwei Wu
Summary: ATF3 plays an anti-tumor role in tongue squamous cell carcinoma (TSCC) cells by negatively regulating its downstream targets IFI6 and IFI27, which suppress cell growth and migration. Understanding ATF3 functions and downstream signaling pathways may lead to the development of new therapeutics for treating tumors like TSCCs.
Editorial Material
Cell Biology
Cord Brakebusch
Editorial Material
Cell Biology
Cord Brakebusch
Article
Cell Biology
Tobias Heib, Heike M. Hermanns, Georgi Manukjan, Maximilian Englert, Charly Kusch, Isabelle Carlotta Becker, Annika Gerber, Lou Martha Wackerbarth, Philipp Burkard, Thomas Dandekar, Johannes Balkenhol, Daniel Jahn, Sarah Beck, Mara Meub, Sebastian Dutting, Christian Stigloher, Markus Sauer, Deya Cherpokova, Harald Schulze, Cord Brakebusch, Bernhard Nieswandt, Zoltan Nagy, Irina Pleines
Summary: The study demonstrates that RhoA/Cdc42 signaling is crucial for platelet precursor formation, and that the polyploidization and cytoplasmic maturation of MKs are separately regulated processes.
Article
Biochemistry & Molecular Biology
Rafael Brandao, Mei Qi Kwa, Yossi Yarden, Cord Brakebusch
Summary: The research found that the lack of the ACK1 gene in mice and breast cancer cell lines does not have a major impact on development, tissue maintenance, tumor formation, and cell migration.
Article
Cell Biology
Mei Qi Kwa, Rafael Brandao, Trong H. Phung, Jianfeng Ge, Giuseppe Scieri, Cord Brakebusch
Summary: MRCK alpha is highly amplified in human breast cancer but its in vivo function remains unclear. Deletion of MRCK alpha did not affect tumor development in mouse models or migration of cancer cells, suggesting limited functional importance despite its potential as a prognostic marker in breast cancer.
Article
Neurosciences
Sina Stern, Brett J. Hilton, Emily R. Burnside, Sebastian Dupraz, Emily E. Handley, Jessica M. Gonyer, Cord Brakebusch, Frank Bradke
Summary: Studies reveal that an inhibitory extracellular environment and neuron-intrinsic processes work together to prevent axon regeneration in the adult central nervous system. Genetic loss-of-function experiments show that the small GTPase RhoA relays extracellular inhibitory signals to the cytoskeleton. Neuronal RhoA restricts axon regeneration by activating myosin II, while astrocytic RhoA limits injury-induced astrogliosis through YAP signaling.
Article
Cell Biology
Fabian Bock, Bertha C. Elias, Xinyu Dong, Diptiben Parekh, Glenda Mernaugh, Olga M. Viquez, Anjana Hassan, Venkateswara Rao Amara, Jiageng Liu, Kyle L. Brown, Andrew S. Terker, Manuel Chiusa, Leslie S. Gewin, Agnes B. Fogo, Cord H. Brakebusch, Ambra Pozzi, Roy Zent
Summary: The study demonstrates that Rac1 is not essential for epithelial branching morphogenesis during kidney collecting duct development, but plays a crucial role in maintaining epithelial integrity, polarity, and function by Arp2/3-dependent cytoskeletal branching. This function of Rac1 involves restricting actomyosin activity. Despite a mild developmental phenotype in mice with selectively deleting Rac1 at the initiation of UB development, aging leads to disruption of epithelial integrity and function in the collecting duct, which is reversible with direct myosin II inhibition. Additionally, Rac1 controls lateral membrane height and overall epithelial morphology by restricting actomyosin and promoting CD epithelial integrity.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Gastroenterology & Hepatology
Luz del Carmen Martinez-Sanchez, Phuong Anh Ngo, Rashmita Pradhan, Lukas-Sebastian Becker, David Boehringer, Despina Soteriou, Marketa Kubankova, Christine Schweitzer, Tatyana Koch, Veronika Thonn, Lena Erkert, Iris Stolzer, Claudia Guenther, Christoph Becker, Benno Weigmann, Monika Klewer, Christoph Daniel, Kerstin Amann, Stefan Tenzer, Raja Atreya, Martin Bergo, Cord Brakebusch, Alastair J. M. Watson, Jochen Guck, Ben Fabry, Imke Atreya, Markus F. Neurath, Rocio Lopez-Posadas
Summary: Abnormal cell shedding is associated with intestinal barrier dysfunction and inflammatory bowel diseases. Deletion of PGGTase and RAC1 in intestinal epithelial cells leads to cell overcrowding and epithelial leakage, resulting in chronic intestinal inflammation. RAC1 plays a crucial role in regulating cytoskeletal dynamics, cell mechanics, and intestinal cell shedding.
Article
Microbiology
Lara Petersen, Svenja Stroh, Dennis Schoettelndreier, Guntram A. Grassl, Klemens Rottner, Cord Brakebusch, Joerg Fahrer, Harald Genth
Summary: Clostridioides difficile infection causes pseudomembranous colitis, characterized by a loss of epithelial barrier function and colonic inflammation. The toxins TcdA and TcdB inhibit colonic stem cell proliferation and regeneration, leading to the development of PMC.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Immunology
Anila Vadakumchery, Hemin Faraidun, Omar El Ayoubi, Issame Outaleb, Vera Schmid, Hend Abdelrasoul, Timm Amendt, Ahmad Khadour, Corinna Setz, Katharina Goehring, Karoline Lodd, Christoffer Hitzing, Alabbas Alkhatib, Mayas Bilal, Julian Benckendorff, Abdul Kader Al Shugri, Cord Herbert Brakebusch, Niklas Engels, Moumita Datta, Elias Hobeika, Ameera Alsadeq, Hassan Jumaa
Summary: The adaptor protein SLP65 controls the down-regulation of PI3K signaling in B cells by inducing the activity of small GTPase RHOA, which activates the negative regulator PTEN. RHOA plays a unique role in B cell generation and selection, and blocking its function offers potential for treating B cell malignancies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Zilu Ye, Gulcan Kilic, Sally Dabelsteen, Irina N. Marinova, Jens F. B. Thofner, Ming Song, Asha M. Rudjord-Levann, Ieva Bagdonaite, Sergey Y. Vakhrushev, Cord H. Brakebusch, Jesper v Olsen, Hans H. Wandall
Summary: This study investigates the importance of TGF-beta signaling pathway in human epithelial tissue homeostasis and transformation. Using genetic engineering, 3D tissue models, and quantitative proteomics, the study reveals that the loss of TGF-beta signaling promotes cell proliferation, delays differentiation, and induces invasive growth. The loss of TGF-beta receptor II (TGF-beta RII) has a stronger impact on cell proliferation and differentiation, and it also affects cell-matrix interactions and activates proinflammatory mediators.
Article
Neurosciences
Ana I. Seixas, Miguel R. G. Morais, Cord Brakebusch, Joao B. Relvas
Summary: Myelin plays a vital role in improving axonal conduction velocity and is essential for nerve development and regeneration. The process of myelin sheath formation in peripheral nerves is not yet fully understood, but it has been found that RhoA is involved in promoting the initiation of myelination and regulating myelin growth at different stages of peripheral myelination. RhoA acts on actin filament turnover, actomyosin contractility, and cortical actin-membrane attachments in Schwann cells, which in turn regulate axon-Schwann cell interaction/adhesion and myelin growth. This study highlights the importance of RhoA in controlling Schwann cell state transitions for proper myelination of peripheral nerves.
PROGRESS IN NEUROBIOLOGY
(2023)
Article
Cell Biology
Renato Socodato, Tiago O. Almeida, Camila C. Portugal, Evelyn C. S. Santos, Joana Tedim-Moreira, Joao Galvao-Ferreira, Teresa Canedo, Filipa I. Baptista, Ana Magalhaes, Antonio F. Ambrosio, Cord Brakebusch, Boris Rubinstein, Irina S. Moreira, Teresa Summavielle, Ines Mendes Pinto, Joao B. Relvas
Summary: This study demonstrates that Rac1 in microglia is crucial for sensing and interpreting the brain microenvironment, as well as for the communication between microglia and synapses that drives experience-dependent plasticity and cognitive performance.
Article
Cell Biology
Marco Kirchenwitz, Jessica Halfen, Kristin von Peinen, Silvia Prettin, Jana Kollasser, Susanne zur Lage, Wulf Blankenfeldt, Cord Brakebusch, Klemens Rottner, Anika Steffen, Theresia E. B. Stradal
Summary: The study found that RhoB is upregulated after Salmonella infection, and it binds to SopB and localizes on early phagosomes of intracellular Salmonella. RhoB is specifically required for Salmonella-induced upregulation of autophagy, promoting the intracellular survival of the bacterium.
EUROPEAN JOURNAL OF CELL BIOLOGY
(2023)