Article
Biology
Valentina Kugler, Andreas Lieb, Nathan Guerin, Bruce R. Donald, Eduard Stefan, Teresa Kaserer
Summary: We introduce an Osprey-based computational protocol that can prospectively identify oncogenic mutations by disrupting molecular interactions. This protocol can be used to analyze protein-protein and protein-DNA interfaces and has been validated on a dataset of clinically relevant mutations. Furthermore, it successfully predicts previously uncharacterized patient mutations in CDK6 and p16 genes, which have been experimentally confirmed to impair complex formation. The Disruptor algorithm evaluates whether mutations disrupt protein-protein and protein-DNA interactions and calculates the relative probabilities of specific mutations, identifying those with a high probability of becoming clinically relevant for carcinogenesis.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Jayanth Kumar Palanichamy, Tiffany M. Tran, Jennifer K. King, Sol Katzman, Alexander J. Ritter, Gunjan Sharma, Christine Tso, Jorge R. Contreras, Thilini R. Fernando, Jeremy R. Sanford, Dinesh S. Rao
Summary: Loss of function in the tumor suppressor gene TP53 is the most common alteration seen in human cancer. In mice, P53 deletion in all cells leads predominantly to the development of T-cell lymphomas, followed by B-cell lymphomas, sarcomas and teratomas. This study demonstrates lineage specific P53 deletion leading to distinct phenotypes secondary to unique gene expression programs set in motion.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Ori Hassin, Nishanth Belugali Nataraj, Michal Shreberk-Shaked, Yael Aylon, Rona Yaeger, Giulia Fontemaggi, Saptaparna Mukherjee, Martino Maddalena, Adi Avioz, Ortal Iancu, Giuseppe Mallel, Anat Gershoni, Inna Grosheva, Ester Feldmesser, Shifra Ben-Dor, Ofra Golani, Ayal Hendel, Giovanni Blandino, David Kelsen, Yosef Yarden, Moshe Oren
Summary: The TP53 gene is frequently mutated in colorectal cancer (CRC) and different mutations have different impacts on cancer progression. Specifically, CRC tumors harboring R273 mutations have a higher likelihood of developing metastatic disease and a worse prognosis compared to those with R175 mutations. Furthermore, these R273 mutations are associated with the activation of oncogenic signaling pathways. This study highlights the importance of understanding the specific TP53 mutations in CRC for precision-based medicine.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Tzitzijanik Madrigal, Daniel Ortega-Bernal, Luis A. Herrera, Claudia Haydee Gonzalez-de la Rosa, Guadalupe Dominguez-Gomez, Elena Arechaga-Ocampo, Jose Diaz-Chavez
Summary: The p53 gene mutations have a negative effect on miRNA expression and induce cell migration and invasion. The upregulation of miR-182-5p is associated with processes such as cell migration and invasion.
Article
Cell Biology
Ambuja Navalkar, Ajoy Paul, Arunima Sakunthala, Satyaprakash Pandey, Amit Kumar Dey, Sandhini Saha, Sarthak Sahoo, Mohit Kumar Jolly, Tushar K. Maiti, Samir K. Maji
Summary: This study reveals that p53 can form amyloids, which disrupt the normal functions of the protein and contribute to cancer development. Targeting key molecules affected by p53 amyloid formation can reverse the oncogenic phenotype and induce apoptosis in cells.
JOURNAL OF CELL SCIENCE
(2022)
Article
Oncology
Eijiro Shimada, Yoshihiro Matsumoto, Makoto Nakagawa, Yosuke Susuki, Makoto Endo, Nokitaka Setsu, Toshifumi Fujiwara, Keiichiro Iida, Akira Nabeshima, Kenichiro Yahiro, Atsushi Kimura, Takeshi Hirose, Masaya Kanahori, Ryunosuke Oyama, Yoshinao Oda, Yasuharu Nakashima
Summary: In dedifferentiated chondrosarcoma, DNA methylation leads to the downregulation of PRKCZ, which prevents apoptosis through the inactivation of the ATM/CHK2 pathway. Decitabine can upregulate the expression of PRKCZ by demethylating its promoter region, providing a potential therapy for dedifferentiated chondrosarcoma.
BRITISH JOURNAL OF CANCER
(2022)
Article
Cell Biology
Wen Deng, Ru Chen, Situ Xiong, Jianqiang Nie, Hailang Yang, Ming Jiang, Bing Hu, Xiaoqiang Liu, Bin Fu
Summary: This study demonstrates that circFSCN1 is upregulated in bladder cancer and associated with cancer-specific survival. CircFSCN1 promotes tumor progression and epithelial-mesenchymal transition in bladder cancer through enhancing MDM2-mediated silencing of p53 by sponging miR-145-5p.
CELLULAR SIGNALLING
(2024)
Article
Multidisciplinary Sciences
Nikola Arsic, Tania Slatter, Gilles Gadea, Etienne Villain, Aurelie Fournet, Marina Kazantseva, Frederic Allemand, Nathalie Sibille, Martial Seveno, Sylvain de Rossi, Sunali Mehta, Serge Urbach, Jean-Christophe Bourdon, Pau Bernado, Andrey Kajava, Antony Braithwaite, Pierre Roux
Summary: The p53 isoform Delta 133p53 beta promotes intrinsic oncogenic functions, with its activity regulated through an aggregation-dependent mechanism. Interaction with partners like p63 family members or the CCT chaperone complex influences cancer cell features such as migration and invasion by modulating Delta 133p53 beta activity.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Madhu Kollareddy, Luis A. Martinez
Summary: Plant-derived compounds tested in this study showed the ability to reduce mutant p53 protein levels and its important targets involved in invasion and metastasis, leading to cell proliferation inhibition. These compounds also downregulated nucleotide metabolism genes and key ETS transcription family members, suggesting a potential multi-pathway inhibition of invasion in triple-negative breast cancer.
Article
Oncology
Asmaa M. Elsherbini, Salah A. Sheweita, Ahmed S. Sultan
Summary: Pterostilbene can reduce the viability and proliferation of mutant p53 breast cancer cells, promote apoptosis, and induce changes in cell morphology and protein expression. These findings demonstrate the potential anticancer effects of PT.
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
(2021)
Article
Pathology
Aysegul Arslan, Sevil Karabag, Murat Akgul
Summary: The present study aimed to identify molecular sub-groups in MIBC cases using an immunohistochemical panel and investigated the expression of HER2/Neu and Fascin in these sub-groups. The results showed that the expression of HER2/Neu in the luminal sub-group and Fascin in the basal and p53-like groups may serve as negative prognostic markers.
INDIAN JOURNAL OF PATHOLOGY AND MICROBIOLOGY
(2022)