Article
Biochemistry & Molecular Biology
Zhiwen Zhu, Dongdong Li, Zeran Jia, Wenhao Zhang, Yuling Chen, Ruixue Zhao, Yan-Ping Zhang, Wen-Hong Zhang, Haiteng Deng, Yinqing Li, Wei Li, Shouhong Guang, Guangshuo Ou
Summary: Eukaryotic organisms adapt to environmental fluctuations by altering their epigenomic landscapes and transcriptional programs. Histone H2Bs are globally degraded in Caenorhabditis elegans during starvation, and the mechanisms underlying this degradation involve ubiquitin and ubiquitin-related enzymes. The retention of aberrant nucleosomal H2Bs leads to abnormal gene expression and impacts animal viability. Furthermore, the ubiquitin-proteasome system regulates chromosomal histone turnover in human cells.
Article
Multidisciplinary Sciences
Jan A. Veenstra
Summary: The study identified a triplet of genes encoding irps in some ambulacrarians, with two being orthologs of arthropod genes. In echinoderms, two new irps emerged from gene duplications, likely from IGF and dilp7-like genes. This suggests that irps produced by neuroendocrine cells in insects and echinoderm GSS may have evolved independently from IGF, indicating convergent evolution.
Article
Biochemistry & Molecular Biology
Niki Sarri, Natalia Papadopoulos, Johan Lennartsson, Carl-Henrik Heldin
Summary: Tripartite motif-containing protein 21 (TRIM21) contributes to the ubiquitination and regulation of basal levels of PDGFR beta in human primary fibroblasts AG1523 and the osteosarcoma cell line U2OS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Niki Sarri, Kehuan Wang, Maria Tsioumpekou, Casimiro Castillejo-Lopez, Johan Lennartsson, Carl-Henrik Heldin, Natalia Papadopoulos
Summary: Interaction between platelet-derived growth factors (PDGF) and their receptors leads to receptor activation and internalization, which is regulated by deubiquitinating enzymes. Deubiquitination of the receptors affects receptor trafficking and stability, as well as downstream signaling and transcription through STAT3, resulting in dysregulated cell proliferation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Julian Bailes, Mikhail Soloviev
Summary: IGF-1, the principal mediator of GH, plays a crucial role in cell growth, differentiation, and apoptosis, with its bioavailability affected by IGFBPs. The varying expression levels of IGF-1 in clinical conditions and its misuse in sports have raised significant concerns.
Review
Biochemistry & Molecular Biology
Sujitha Jayaprakash, Mangala Hegde, Bandari BharathwajChetty, Sosmitha Girisa, Mohammed S. Alqahtani, Mohamed Abbas, Gautam Sethi, Ajaikumar B. Kunnumakkara
Summary: Cancer is a deadly disease that is strongly related to genetic changes and post-translational modifications. The E3 ubiquitin ligases, particularly NEDD4, play a crucial role in regulating cellular processes by controlling protein degradation and substrate ubiquitination. NEDD4 has both tumor-suppressive and oncogenic roles in various malignancies. This review summarizes the function of NEDD4 in cancer development, including its role in cell survival, proliferation, autophagy, migration, invasion, metastasis, epithelial-mesenchymal transition, chemoresistance, and multiple signaling pathways. Additionally, the significance of NEDD4 as a potential target for cancer treatment is discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Elizaveta Rabushko, Maxim Sorokin, Maria Suntsova, Alexander P. Seryakov, Denis Kuzmin, Elena Poddubskaya, Anton A. Buzdin
Summary: This study identified potential clinically relevant RTK fusions by annotating RNAseq reads, providing a basis for automatic annotation of 3' RTK fusions using FFPE RNAseq profiles.
Review
Cell Biology
Shudong Zhu, Rong Sun, Xialing Guo, Yuanwu Bao, Dianzheng Zhang
Summary: This article summarizes the important roles of Src family kinases (SFKs) in multiple signaling pathways, with a focus on the inhibitory function of CHK in tumor development and its regulation of various substrates. Although the precise functions of CHK are still unclear, it has been found to allosterically inhibit Src kinase activity and is regulated through promoter methylation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Yuhan Zhu, Lin Chen, Binyu Song, Zhiwei Cui, Guo Chen, Zhou Yu, Baoqiang Song
Summary: The article describes the expression changes and fibrosis-promoting effects of insulin-like growth factor 2 (IGF-2) in different tissues during fibrosis process.
Article
Oncology
Bunpei Miyazaki, Toshihide Ueno, Masanaka Sugiyama, Shinya Kojima, Ayumu Arakawa, Kayoko Tao, Kazuki Tanimura, Kouya Shiraishi, Shigehiro Yagishita, Shinji Kohsaka, Mamoru Kato, Nobutaka Kiyokawa, Yasushi Goto, Yasushi Yatabe, Akinobu Hamada, Hiroyuki Mano, Chitose Ogawa, Yosuke Tanaka
Summary: We identified a novel fusion gene pattern NRIP1::PDGFRB in Ph-like ALL, which showed oncogenic potential in pediatric patients. The study also confirmed the inhibitory effect of multiple ABL1-specific inhibitors on this fusion gene.
NPJ PRECISION ONCOLOGY
(2023)
Article
Oncology
Ying-Chen Chen, Chu-Yen Chien, Chia-Chen Hsu, Chien-Hsing Lee, Yu-Ting Chou, Shine-Gwo Shiah, Shyun-Yeu Liu, Ching-Yu Yen, Alexander Cheng-Ting Hsieh, Martin Wabitsch, Yi-Shing Shieh
Summary: This study demonstrates that leptin-mediated AXL signaling pathway activation contributes to 5-FU resistance in colorectal cancer, suggesting a novel therapeutic strategy for colorectal cancer treatment.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Immunology
Yue Yang, Mingxia Yao, Jie Zeng, Dongwang Zheng, Qin Li, Ya Ni, Xiang Xiao
Summary: FYN plays an important role in maintaining the integrity of the blood-testis barrier and the adhesion of germ cells to Sertoli cells. It is structurally linked to the actin and microtubule-based cytoskeletons. The study suggests that FYN and Arp3 form a protein complex that regulates junction reorganization events at the apical ectoplasmic specialization and the blood-testis barrier, and this mechanism may also allow viruses to enter the immunoprivileged testicular microenvironment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Ji Hyun Lee, Su-Jin Shin, Eun-Ah Choe, Jungyoun Kim, Woo Jin Hyung, Hyo Song Kim, Minkyu Jung, Seung-Hoon Beom, Tae Il Kim, Joong Bae Ahn, Hyun Cheol Chung, Sang Joon Shin
Summary: This study analyzed the incidence of NTRK fusion in KIT/PDGFRA wild-type GISTs and found that 16% of cases in the Yonsei Cancer Center had NTRK fusion. The confirmation of NTRK fusion in KIT/PDGFRA wild-type GISTs provides important information for improving therapeutic outcomes and suggests further research to improve methods for identifying this disease subtype.
Review
Pathology
Minh Anh Nguyen, Andrew J. Colebatch, Diana Van Beek, Geraldine Tierney, Ruta Gupta, Wendy A. Cooper
Summary: Fusions involving the NTRK gene family are targetable oncogenic alterations found in a diverse range of tumors. Identifying these fusions is challenging due to various genetic mechanisms, frequency differences, and other factors. Pathologists play a key role in determining optimal testing approaches with therapeutic and prognostic implications. This review provides an overview of tumors harboring NTRK fusions and available testing methods.
Review
Biochemistry & Molecular Biology
Vignesh Sivaganesh, Varsha Sivaganesh, Christina Scanlon, Alexander Iskander, Salma Maher, Thu Le, Bela Peethambaran
Summary: Protein tyrosine phosphatases (PTPs) have emerged as a new target in cancer therapy, with both tumor-suppressive and oncogenic properties. This review focuses on key PTPs investigated in various cancers and explores the different mechanisms underlying pro-cancerous and anti-cancerous effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Alexander Drilon, Chelsea Jenkins, Sudarshan Iyer, Adam Schoenfeld, Clare Keddy, Monika A. Davare
Summary: The proto-oncogene ROS1 encodes a receptor tyrosine kinase without a well-defined physiological role, and somatic chromosomal fusions involving ROS1 lead to chimeric oncoproteins that drive various cancers. Although ROS1-directed tyrosine kinase inhibitors show therapeutic efficacy, resistance mechanisms remain unclear.
NATURE REVIEWS CLINICAL ONCOLOGY
(2021)
Article
Oncology
Ezra Y. Rosen, Melissa L. Johnson, Sarah E. Clifford, Romel Somwar, Jennifer F. Kherani, Jieun Son, Arrien A. Bertram, Monika A. Davare, Eric Gladstone, Elena Ivanova, Dahlia N. Henry, Elaine M. Kelley, Mika Lin, Marina S. D. Milan, Binoj C. Nair, Elizabeth A. Olek, Jenna E. Scanlon, Morana Vojnic, Kevin Ebata, Jaclyn F. Hechtman, Bob T. Li, Lynette M. Sholl, Barry S. Taylor, Marc Ladanyi, Pasi A. Janne, S. Michael Rothenberg, Alexander Drilon, Geoffrey R. Oxnard
Summary: The RET proto-oncogene is activated by gene fusion in 1%-2% of NSCLC, while MET amplification is associated with resistance to selpercatinib. Combination therapy with selpercatinib and crizotinib can overcome MET-mediated resistance to RET inhibition.
CLINICAL CANCER RESEARCH
(2021)
Article
Cell Biology
Takuo Hayashi, Igor Odintsov, Roger S. Smith, Kota Ishizawa, Allan J. W. Liu, Lukas Delasos, Christopher Kurzatkowski, Huichun Tai, Eric Gladstone, Morana Vojnic, Shinji Kohsaka, Ken Suzawa, Zebing Liu, Siddharth Kunte, Marissa S. Mattar, Inna Khodos, Monika A. Davare, Alexander Drilon, Emily Cheng, Elisa de Stanchina, Marc Ladanyi, Romel Somwar
Summary: The study demonstrates that cabozantinib is effective in targeting lung cancers with RET rearrangements by inhibiting tumor growth and activating specific apoptotic pathways. Additionally, cabozantinib suppresses MYC protein levels induced by RET expression, suggesting new therapeutic strategies for RET fusion-driven lung cancers. The novel RET fusion-dependent preclinical models offer valuable tools for refining current therapies and exploring new treatment approaches.
DISEASE MODELS & MECHANISMS
(2021)
Article
Oncology
Neil M. Iyengar, Xi Kathy Zhou, Hillary Mendieta, Dilip D. Giri, Omar El-Hely, Lisle Winston, Domenick J. Falcone, Hanhan Wang, Lingsong Meng, Jonathan Landa, Michael Pollak, Laurie Kirstein, Monica Morrow, Andrew J. Dannenberg
Summary: Excess body fat and sedentary behavior are associated with increased breast cancer risk and mortality. The study found that adiposity and lack of exercise impact the breast microenvironment and circulating metabo-inflammatory factors, suggesting the importance of lifestyle interventions targeting adiposity to prevent tumor growth.
CANCER PREVENTION RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Sirui Zhou, Guillaume Butler-Laporte, Tomoko Nakanishi, David R. Morrison, Jonathan Afilalo, Marc Afilalo, Laetitia Laurent, Maik Pietzner, Nicola Kerrison, Kaiqiong Zhao, Elsa Brunet-Ratnasingham, Danielle Henry, Nofar Kimchi, Zaman Afrasiabi, Nardin Rezk, Meriem Bouab, Louis Petitjean, Charlotte Guzman, Xiaoqing Xue, Chris Tselios, Branka Vulesevic, Olumide Adeleye, Tala Abdullah, Noor Almamlouk, Yiheng Chen, Michael Chasse, Madeleine Durand, Clare Paterson, Johan Normark, Robert Frithiof, Miklos Lipcsey, Michael Hultstrom, Celia M. T. Greenwood, Hugo Zeberg, Claudia Langenberg, Elin Thysell, Michael Pollak, Vincent Mooser, Vincenzo Forgetta, Daniel E. Kaufmann, J. Brent Richards
Summary: The study identified that increased levels of OAS1 protein are associated with reduced susceptibility and severity of COVID-19, providing evidence for a protective role of OAS1 in adverse outcomes. This suggests that pharmacological agents that increase OAS1 levels could be prioritized for drug development against COVID-19. The variant of the OAS1 gene associated with decreased risk of death in COVID-19 patients encodes an enzyme critical for the innate immune response to viral infections.
Article
Oncology
Byuri Angela Cho, Neil M. Iyengar, Xi Kathy Zhou, Monica Morrow, Dilip D. Giri, Akanksha Verma, Olivier Elemento, Michael Pollak, Andrew J. Dannenberg
Summary: Obesity and breast white adipose tissue inflammation are associated with increased risk of post-menopausal breast cancer. Through analyzing molecular changes in breast tissues and blood biomarkers, this study helps to explain the link between obesity and breast cancer, highlighting the potential utility of blood biomarkers in determining risk and prognosis.
Article
Biochemistry & Molecular Biology
Sebastian Igelmann, Frederic Lessard, Oro Uchenunu, Jacob Bouchard, Ana Fernandez-Ruiz, Marie-Camille Rowell, Stephane Lopes-Paciencia, David Papadopoli, Aurelien Fouillen, Katia Julissa Ponce, Genevieve Huot, Lian Mignacca, Mehdi Benfdil, Paloma Kalegari, Haytham M. Wahba, Jan Pencik, Nhung Vuong, Jordan Quenneville, Jordan Guillon, Veronique Bourdeau, Laura Hulea, Etienne Gagnon, Lukas Kenner, Richard Moriggl, Antonio Nanci, Michael N. Pollak, James G. Omichinski, Ivan Topisirovic, Gerardo Ferbeyre
Summary: A multi-enzymatic complex, known as hydride transfer complex (HTC), is reported to reprogram NAD metabolism and overcome cellular senescence in cancer or hypoxic cells. This complex is highly expressed in prostate cancer models and its inactivation triggers senescence, while its exogenous expression can bypass senescence and cooperate with oncogenic RAS to transform primary cells.
Article
Multidisciplinary Sciences
Stephanie P. Totten, Young Kyuen Im, Eduardo Cepeda Canedo, Ouafa Najyb, Alice Nguyen, Steven Hebert, Ryuhjin Ahn, Kyle Lewis, Benjamin Lebeau, Rachel La Selva, Valerie Sabourin, Constanza Martinez, Paul Savage, Hellen Kuasne, Daina Avizonis, Nancy Santos Martinez, Catherine Chabot, Adriana Aguilar-Mahecha, Marie-Line Goulet, Matthew Dankner, Michael Witcher, Kevin Petrecca, Mark Basik, Michael Pollak, Ivan Topisirovic, Rongtuan Lin, Peter M. Siegel, Claudia L. Kleinman, Morag Park, Julie St-Pierre, Josie Ursini-Siegel
Summary: Bioenergetic perturbations and oxidative stress play important roles in promoting neoplastic growth, requiring compensatory increase in ROS scavengers. In addition, inflammatory mediators can enhance drug cytotoxicity through STAT1-mediated downregulation of ROS scavengers.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Stephanie M. Wong, Lissa Ajjamada, Anna C. Weiss, Ipshita Prakash, Sonia Skamene, Jean Francois Boileau, Michael N. Pollak, Mark Basik
Summary: Breast cancers in women who previously received radiation therapy for HL are characterized by earlier onset disease, although most remain estrogen receptor-positive and have early stage disease at presentation.
Article
Oncology
Talia Malagon, Jean H. E. Yong, Parker Tope, Wilson H. Miller, Eduardo L. Franco
Summary: This study used a microsimulation model to estimate the long-term impacts of cancer care disruptions during the COVID-19 pandemic in Canada. It predicted over 21,000 additional cancer deaths between 2020 and 2030, with the potential to mitigate these losses by increasing diagnostic and treatment capacity in the short term.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Oncology
Manu Prasad, Jonathan Zorea, Sankar Jagadeeshan, Avital B. Shnerb, Sooraj Mathukkada, Jebrane Bouaoud, Lucas Michon, Ofra Novoplansky, Mai Badarni, Limor Cohen, Ksenia M. Yegodayev, Sapir Tzadok, Barak Rotblat, Libor Brezina, Andreas Mock, Andy Karabajakian, Jerome Fayette, Idan Cohen, Tomer Cooks, Irit Allon, Orr Dimitstein, Benzion Joshua, Dexin Kong, Elena Voronov, Maurizio Scaltriti, Yaron Carmi, Cristina Conde-Lopez, Jochen Hess, Ina Kurth, Luc G. T. Morris, Pierre Saintigny, Moshe Elkabets
Summary: In head and neck cancer, treatment with MEK1/2 inhibitor delays tumor progression and enhances antitumor immunity of CD8(+) T cells. Sensitizing tumors to immunotherapy during MEK1/2 inhibition can eliminate tumors and induce immune memory. Prolonged treatment with MEK1/2 inhibitor may lead to immunosuppressive tumor microenvironment due to epithelial to mesenchymal transition.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Medicine, Research & Experimental
Sudarshan R. Iyer, Kevin Nusser, Kristen Jones, Pushkar Shinde, Clare Keddy, Catherine Z. Beach, Erin Aguero, Jeremy Force, Ujwal Shinde, Monika A. Davare
Summary: ROS1 gene rearrangements result in oncogenic ROS1 kinase fusion proteins, which are currently the only validated biomarkers for targeted therapy with ROS1 TKIs. We identified 34 missense mutations in the ROS1 tyrosine kinase domain and found that they have varying effects on ROS1 kinase function, including loss and increased catalytic activity. Specific point mutations within the ROS1 kinase domain, such as Asn and Gly substitutions at Asp2113, were found to be TKI-sensitive oncogenic variants. These findings demonstrate the potential of targeting these mutations with FDA-approved ROS1-TKIs.
EMBO MOLECULAR MEDICINE
(2023)
Article
Biology
Mai Badarni, Shani Gabbay, Moshe Elkabets, Barak Rotblat
Summary: Mitochondria, the energy-producing organelles of a cell, contain enzymes that are essential for cellular processes. Proper folding of these enzymes is facilitated by chaperones. This study investigates the relationship between specific mitochondrial chaperones, drug sensitivity in tumor cells, and the folding of mitochondrial proteins.
Article
Oncology
Brendan J. Guercio, Sui Zhang, Fang-Shu Ou, Alan P. Venook, Donna Niedzwiecki, Heinz-Josef Lenz, Federico Innocenti, Michael N. Pollak, Andrew B. Nixon, Brian C. Mullen, Bert H. O'Neil, James E. Shaw, Blase N. Polite, Al Bowen Benson, James N. Atkins, Richard M. Goldberg, Justin C. Brown, Eileen M. O'Reilly, Robert J. Mayer, Charles D. Blanke, Charles S. Fuchs, Jeffrey A. Meyerhardt
Summary: In patients with metastatic colorectal cancer, high levels of plasma IGFBP-3 and low levels of IGFBP-7 were associated with longer overall survival and progression-free survival. Extreme levels of adiponectin were linked to shorter progression-free survival, suggesting potential implications for prognostic and therapeutic innovation.
JNCI CANCER SPECTRUM
(2021)
Article
Chemistry, Multidisciplinary
Jonathan C. Savage, Pushkar Shinde, Yizhou Yao, Monika A. Davare, Ujwal Shinde
Summary: By creating a chimera of Broccoli RNAs with mixed chemistries, it is possible to develop an effective RNA-based fluorescent K+ sensor that maintains structure and fluorescence properties without interference, providing linear fluorescent gain across physiological K+ concentrations.
CHEMICAL COMMUNICATIONS
(2021)