Article
Oncology
Francesca Liccardo, Martyna Sniegocka, Claudia Tito, Alessia Iaiza, Tiziana Ottone, Mariadomenica Divona, Serena Travaglini, Maurizio Mattei, Rosella Cicconi, Selenia Miglietta, Giuseppe Familiari, Stefania Annarita Nottola, Vincenzo Petrozza, Luca Tamagnone, Maria Teresa Voso, Silvia Masciarelli, Francesco Fazi
Summary: In this study, a combination therapy of low doses of retinoic acid (R), bortezomib (B), and arsenic trioxide (A) was found to induce proteotoxic stress and oxidative stress in FLT3-ITD+ AML cells, resulting in strong cytotoxic activity. The protective role of bone marrow stromal cells (BMSCs) in AML cells was also demonstrated, but this protection can be overcome by using high doses of ascorbic acid (Vitamin C) as an adjuvant. Importantly, the combination of RBA and ascorbic acid significantly prolonged the lifespan of a murine model of FLT3-ITD+ AML without toxic effects.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Mahamat Babagana, Lorin R. Brown, Hannah Z. Slabodkin, Julia V. Kichina, Eugene S. Kandel
Summary: Hyperactivity of AKT in cancer cells leads to increased sensitivity to proteotoxic stress, manifested by heightened response to heat shock and greater dependence on XBP1 for growth. This stress-induced vulnerability can be exploited for therapeutic targeting.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jaclyn M. Einstein, Mark Perelis, Isaac A. Chaim, Jitendra K. Meena, Julia K. Nussbacher, Alexandra T. Tankka, Brian A. Yee, Heyuan Li, Assael A. Madrigal, Nicholas J. Neill, Archana Shankar, Siddhartha Tyagi, Thomas F. Westbrook, Gene W. Yeo
Summary: RNA-binding proteins (RBPs) play crucial roles in post-transcriptional gene expression regulation, and disrupting YTHDF2-dependent mRNA degradation can induce apoptosis in triple-negative breast cancer (TNBC) cells and tumors. Our study identified 57 RBP candidates with distinct functions in supporting MYC-driven oncogenic pathways, highlighting the therapeutic potential of RBPs, especially YTHDF2, in counteracting global mRNA synthesis in MYC-driven breast cancers.
Article
Medicine, Research & Experimental
Rana Gharahkhani, Marjan Pourhadi, Niloufar Sadat Mirdamadi, Nasim Dana, Laleh Rafiee, Reza Nedaeinia, Shaghayegh Haghjooy Javanmard
Summary: This study aimed to investigate the effect of anti-podoplanin antibody on U87MG glioma cell lines. The results showed that the anti-podoplanin antibody reduced cell viability and migration, and decreased cell-platelet aggregation. Therefore, blocking podoplanin may represent a promising therapeutic approach for glioblastoma multiforme cancer therapy.
ARCHIVES OF MEDICAL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Marie Pariollaud, Lara H. Ibrahim, Emanuel Irizarry, Rebecca M. Mello, Alanna B. Chan, Brian J. Altman, Reuben J. Shaw, Michael J. Bollong, R. Luke Wiseman, Katja A. Lamia
Summary: Chronic circadian disruption increases tumor burden in a mouse model of lung cancer through enhanced expression and nuclear accumulation of HSF1.
Article
Oncology
Zhen Lu, Eun-Ah Bae, Ioannis I. Verginadis, Hongru Zhang, Christina Cho, Noreen McBrearty, Subin S. George, J. Alan Diehl, Constantinos Koumenis, Linda M. Bradley, Serge Y. Fuchs
Summary: The immune suppressive factors in the tumor microenvironment can weaken the viability and activities of CD8 + T cells, and activating transcription factor-4 (ATF4) plays an important role in maintaining the survival and activities of CD8 + T cells in the tumor microenvironment.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Review
Cell Biology
Morgane Lallier, Louise Marchandet, Brice Moukengue, Celine Charrier, Marc Baud'huin, Franck Verrecchia, Benjamin Ory, Francois Lamoureux
Summary: Osteosarcoma is the most common form of primary bone tumor affecting children and young adults, with a 5-year survival rate of 70%. Heat Shock Proteins play a significant role in cell proliferation, apoptosis inhibition, migration, and drug resistance in osteosarcoma. By studying HSP27, HSP60, HSP70, and HSP90, they can serve as potential clinical uses in osteosarcoma.
Review
Biochemistry & Molecular Biology
Mitsuaki Fujimoto, Ryosuke Takii, Akira Nakai
Summary: Environmental, physiological, and pathological stimuli induce protein misfolding, resulting in aggregation and amyloid fibril formation. To cope with proteotoxic stress, cells have adaptive mechanisms involving changes in gene expression. The heat shock response is a conserved mechanism regulated by heat shock transcription factor 1 (HSF1) in mammals. This article introduces the mechanisms by which HSF1 tightly controls the transcription of heat shock proteins (HSPs) under proteotoxic stress by regulating pre-initiation complex recruitment in their promoters.
Article
Cell Biology
Ting Yu, Xiaofang Yang, Qiang Fu, Junyu Liang, Xinger Wu, Junli Sheng, Yitian Chen, Lu Xiao, Yuxia Wu, Dingnai Nie, Xiaolong You, Haiyan Mai, Kang Chen, Shengfeng Hu
Summary: This study reveals that TRIM11 negatively regulates regulatory T (Treg) cell differentiation in CD4+ T cells and promotes the development of autoimmune diseases in an AIM2-dependent manner. TRIM11 interacts with AIM2 and promotes its selective autophagic degradation by inducing AIM2 ubiquitination and binding to p62. The degradation of AIM2 attenuates AKT and FOXO1 phosphorylation, MYC signaling, and glycolysis, thereby promoting the stability of Treg cells during experimental autoimmune encephalomyelitis (EAE).
Article
Biochemistry & Molecular Biology
Shahrazad Sulaiman, Kholoud Arafat, Aya Mudhafar Al-Azawi, Noura Abdulraouf AlMarzooqi, Shamsa Nasser Ali Hussain Lootah, Samir Attoub
Summary: Despite advances in targeted- and immuno-therapies, lung and breast cancer remain the top two cancers in terms of incidence and mortality. This study investigated the anti-cancer potential of butein, a flavonoid, on lung and breast cancer cells, alone and in combination with frondoside-A. Butein showed significant anti-cancer effects, including inhibition of cell viability, colony growth, migration, and invasion. Combining butein with frondoside-A had additive effects and synergistically inhibited the migration of endothelial cells. Further animal studies are warranted to confirm the relevance of this combination in cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Ritwick Sawarkar
Summary: Cells under proteotoxic stress reduce the expression of many active genes while increasing the expression of stress-response genes. This strategy is similar to the general lockdown response in the COVID-19 pandemic. The mechanism of global transcriptional downregulation, known as stress-induced transcriptional attenuation (SITA), is still being explored. The decrease in RNA and protein production during stress may help maintain proteostasis and allow cells to cope with stress-induced damage. Investigating the role of SITA in diseases caused by proteotoxicity is crucial for the development of potential novel therapeutics.
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
Article
Medicine, General & Internal
Trishan Vaikunthanathan, Emmanuelle Landmann, Diana Marin Correa, Marco Romano, Silvia Cellone Trevelin, Qi Peng, Elena Crespo, Mauro Corrado, Juan-Jose Lozano, Erika L. Pearce, Elena Perpinan, Anna Zoccarato, Leonard Siew, Joy Edwards-Hicks, Reenam Khan, Nguyet-Thin Luu, Mark R. Thursz, Philip N. Newsome, Marc Martinez-Llordella, Naina Shah, Robert I. Lechler, Ajay M. Shah, Alberto Sanchez-Fueyo, Giovanna Lombardi, Niloufar Safinia
Summary: This study reveals that functional redox homeostasis is crucial for the function, stability, and survival of regulatory T cells (Tregs). Targeting Treg-specific antioxidant pathways may have therapeutic potential to reverse Treg impairment in conditions of oxidative damage such as advanced liver disease.
Article
Plant Sciences
Kenji Nishimura, Reiko Nakagawa, Chisato Hachisuga, Yuri Nakajima Munekage
Summary: Our study investigated the heat-dependent thylakoid FtsH protease substrates and the proteotoxicity caused by thermal damage and dysfunctional protease on the thylakoid membrane. We found that carbonylated stromal proteins may be potential targets of FtsH, and observed an upregulation of heat shock proteins and chaperones in the absence of FtsH, indicating a damaged protein response. Interestingly, high-density fractions of thylakoid-enriched proteins included translation factors, RNA-binding proteins, and extraplastid proteins, suggesting an intracellular adaptation to proteotoxic influences.
Review
Oncology
Anna M. Cyran, Anatoly Zhitkovich
Summary: The fitness of cells depends on the maintenance of protein homeostasis, which is achieved through the cooperative activities of protein chaperones and proteolytic machinery. In response to protein-damaging conditions, cells activate the heat-shock response (HSR) by upregulating a group of chaperones known as heat shock proteins (HSPs). Cancer cells, which experience high levels of proteotoxic stress, often upregulate major components of HSR, including HSF1 and individual HSPs. Elevated levels of HSPs and HSF1 are associated with drug resistance and poor clinical outcomes in various types of cancer. Targeting protein quality controls represents a promising approach for the treatment of human malignancies, as it can enhance the efficacy of standard and targeted chemotherapy as well as immune checkpoint inhibitors. In cancers with specific dependencies, HSR components can serve as alternative targets to oncogenic drivers that are difficult to drug.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Deniz Kuscuoglu, Lisa Bewersdorf, Kathrin Wenzel, Annika Gross, Gokce Kobazi Ensari, Yizhao Luo, Konrad Kilic, Kanishka Hittatiya, Nicole Golob-Schwarzl, Rudolf E. Leube, Christian Preisinger, Jacob George, Mayada Metwally, Mohammed Eslam, Pietro Lampertico, Salvatore Petta, Alessandra Mangia, Thomas Berg, Andre Boonstra, Willem P. Brouwer, Maria Lorena Abate, Alessandro Loglio, Angela Sutton, Pierre Nahon, Benedikt Schaefer, Heinz Zoller, Elmar Aigner, Christian Trautwein, Johannes Haybaeck, Pavel Strnad
Summary: The simultaneous presence of two prevalent proteotoxic stresses promotes liver injury development via protein retention and activation of the p62-Nrf2 axis. Specifically, HBs-PiZ mice showed retention of AAT/HBs, leading to accumulation of p62 and perilipin-2, resulting in activation of the p62-Nrf2 axis and generation of reactive oxygen species.
JOURNAL OF PATHOLOGY
(2021)
Article
Biochemistry & Molecular Biology
L. Chen, S. Xu, Y. Xu, W. Lu, L. Liu, D. Yue, J. Teng, J. Chen
Article
Cell Biology
Liang Chen, Michael D. Brewer, Lili Guo, Ruoxing Wang, Peng Jiang, Xiaolu Yang
Article
Multidisciplinary Sciences
Liang Chen, Guixin Zhu, Eleanor M. Johns, Xiaolu Yang
NATURE COMMUNICATIONS
(2018)
Article
Cell Biology
L. Chen, S. Xu, L. Liu, X. Wen, Y. Xu, J. Chen, J. Teng
CELL DEATH & DISEASE
(2014)
Article
Multidisciplinary Sciences
Yanfeng Liu, Shishi Tao, Lijuan Liao, Yang Li, Hongchang Li, Zhihuan Li, Lilong Lin, Xiaochun Wan, Xiaolu Yang, Liang Chen
NATURE COMMUNICATIONS
(2020)
Article
Cell Biology
Lijuan Liao, Deyu Duan, Yanfeng Liu, Liang Chen
Article
Oncology
Jianchao Zhang, Xiaokai Fan, Lijuan Liao, Yan Zhu, Xiaochun Wan, Hai Rao, Liang Chen
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Letter
Oncology
Yanfeng Liu, Yingying Xu, Fan Wang, Yu Tong, Hongchang Li, Xiaochun Wan, Xiaolu Yang, Liang Chen
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Yan Zhu, Lukman O. Afolabi, Xiaochun Wan, Joong Sup Shim, Liang Chen
Summary: Neurodegenerative diseases are characterized by the degeneration of the central or peripheral nervous systems and the aggregation of misfolded proteins, leading to cellular dysfunction and brain damage. TRIM proteins play important roles in maintaining protein quality control and clearing misfolded protein aggregates associated with neurodegenerative diseases.
Article
Oncology
Xuejia Feng, Gui Yang, Litian Zhang, Shishi Tao, Joong Sup Shim, Liang Chen, Qingxia Wu
Summary: This study identified the role of tripartite motif-containing protein 59 (TRIM59) in preventing drug resistance in colorectal cancer (CRC) cells treated with Bortezomib (BTZ). Depletion of TRIM59 enhances endoplasmic reticulum stress and unfolded protein response (UPR) signaling, while also strengthening endoplasmic reticulum-associated degradation (ERAD) and alleviating ROS generation. Knockdown of TRIM59 synergizes with the anti-cancer effect of BTZ both in vitro and in vivo.
INVESTIGATIONAL NEW DRUGS
(2022)
Review
Immunology
Lukman O. Afolabi, Mariam O. Afolabi, Musbahu M. Sani, Wahab O. Okunowo, Dehong Yan, Liang Chen, Yaou Zhang, Xiaochun Wan
Summary: The use of CRISPR-Cas9 technology in cancer research and treatment, particularly in immunotherapy, has shown great potential for innovative cell design and therapy. This technology enables the creation of advanced engineered immune cells with enhanced functionality for better sensing and targeting of tumors.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2021)
