Article
Biochemistry & Molecular Biology
Gehan Botrus, Richard M. Miller, Pedro Luiz Serrano Uson Jr, Geoffrey Kannan, Haiyong Han, Daniel D. Von Hoff
Summary: High levels of ER stress and UPR activation are present in pancreatic cancer, leading to adaptive mechanisms and potential apoptosis. This review discusses the mechanisms by which compounds activate the UPR pathways and induce apoptosis, and explores the potential of ER stress inducers for anti-tumor efficacy in pancreatic cancer. A new approach of increasing ER stress and UPR activation to incite apoptotic cell death in pancreatic cancer is hypothesized.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Gregorio Bonsignore, Simona Martinotti, Elia Ranzato
Summary: The unfolded protein response (UPR) is an adaptive response triggered by endoplasmic reticulum (ER) stress for re-establishing protein homeostasis. Specific ER proteins mediate UPR activation by dissociating from chaperone Glucose-Regulated Protein 78 (GRP78). UPR can decrease ER stress, produce an ER adaptive response, block UPR if ER homeostasis is restored, or regulate apoptosis. This review focuses on molecules that target ER stress and demonstrate how UPR could be a new target in cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jonathan Turpin, Daed El-Safadi, Gregorie Lebeau, Etienne Frumence, Philippe Despres, Wildriss Viranaicken, Pascale Krejbich-Trotot
Summary: Zika virus manipulates cellular responses to delay apoptosis and optimize virus production; by impairing the expression of CHOP/DDIT3 at a translational level, ZIKV inhibits ER stress-driven apoptosis; ZIKV relies on cellular machinery and the unfolded protein response to complete its viral cycle, posing a threat to human health.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Yasuhisa Murai, Ukhyun Jo, Junko Murai, Lisa M. Jenkins, Shar-Yin N. Huang, Sirisha Chakka, Lu Chen, Ken Cheng, Shinsaku Fukuda, Naoko Takebe, Yves Pommier
Summary: The study reveals that SLFN11 deficiency induces proteotoxic stress and sensitizes cancer cells to TAK-243, suggesting that profiling SLFN11 status can serve as a therapeutic biomarker for cancer therapy.
Article
Biochemistry & Molecular Biology
Huimin Zhou, Kexin Wang, Mengyan Wang, Wenxia Zhao, Conghui Zhang, Meilian Cai, Yuhan Qiu, Tianshu Zhang, Rongguang Shao, Wuli Zhao
Summary: This article comprehensively introduces the relationship between ER-phagy and cancer, as well as their molecular mechanism and regulatory pathways. The study finds that ER-phagy plays a significant role in tumor occurrence and maintenance, and may serve as a potential target for cancer therapy.
Article
Biochemistry & Molecular Biology
Yiwei Xu, Jie Chen, Jianguo Chen, Junlin Teng
Summary: In endoplasmic reticulum stress, EI24 protein promotes cell adaptation to ER stress by coordinating the unfolded protein response and calcium signaling, thus playing a role in anti-apoptosis.
Article
Multidisciplinary Sciences
Amanda K. Casey, Hillery F. Gray, Suneeta Chimalapati, Genaro Hernandez, Andrew T. Moehlman, Nathan Stewart, Hazel A. Fields, Burak Gulen, Kelly A. Servage, Karoliina Stefanius, Aubrie Blevins, Bret M. Evers, Helmut Kramer, Kim Orth
Summary: Protein homeostasis is crucial for cellular health, and imbalanced unfolded protein response (UPR) can lead to inflammation and cellular damage. The enzyme filamentation induced by cyclic-AMP (Fic) modulates UPR response by posttranslational modification of binding immunoglobulin protein (BiP). Loss of Fic affects vision, UPR activation, and stress recovery. This study highlights the importance of Fic-mediated AMPylation in the mammalian pancreas during physiological stress.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Mercedes Viettri, Jose L. Zambrano, Romel Rosales, Gerson I. Caraballo, Ana Lorena Gutierrez-Escolano, Juan E. Ludert
Summary: The study investigated whether infection with dengue and Zika viruses triggers a Golgi stress response in vertebrate and mosquito cells, showing that these viruses induce expansion of the Golgi complex and activation of the TFE3 pathway.
SCIENTIFIC REPORTS
(2021)
Review
Pathology
Elmira Aboutalebi Vand Beilankouhi, Mir Amirhossein Sajadi, Iraj Alipourfard, Peyman Hassani, Mohammad Valilo, Reza Safaralizadeh
Summary: When misfolded or unfolded proteins accumulate in the endoplasmic reticulum (ER) due to stress, the unfolded protein response (UPR) is activated. This process is disrupted in various diseases including diabetes, neurodegenerative diseases, and cancers. The UPR activates specific signaling pathways in the ER, nucleus, and cytoplasm to restore cellular homeostasis, either promoting cell survival or apoptosis. Disturbance in this balance can lead to cancer.
PATHOLOGY RESEARCH AND PRACTICE
(2023)
Article
Biochemistry & Molecular Biology
Song Su, Yan-Ting Shi, Yi Chu, Ming-Zuo Jiang, Nan Wu, Bing Xu, He Zhou, Jun-Chao Lin, Yi-Rong Jin, Xiao-Fei Li, Jie Liang
Summary: Sec62 is upregulated in gastric cancer and acts as an independent predictor of poor prognosis. Sec62 promotes migration and invasion of gastric cancer cells through regulating the balance of TIMP-1 and MMP2/9. Moreover, Sec62 can activate autophagy to facilitate gastric cancer metastasis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Cell Biology
Shreya Das, Arunima Mondal, Jayeeta Samanta, Santanu Chakraborty, Arunima Sengupta
Summary: The endoplasmic reticulum orchestrates the production of secretory and membrane proteins, with stress often related to disruption in protein folding. Mild stress can be reversed, but acute stress activates the unfolded protein response leading to protective or pro-apoptotic responses. When stress surpasses the response, cell apoptosis prevails, contributing to various diseases.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2021)
Article
Oncology
Halima Alsamri, Aysha Alneyadi, Khalid Muhammad, Mohammed Akli Ayoub, Ali Eid, Rabah Iratni
Summary: In this study, it was found that carnosol induces apoptotic and autophagic cell death in breast cancer cells through ROS-dependent ER stress, demonstrating its anti-malignant activity.
FRONTIERS IN ONCOLOGY
(2022)
Review
Neurosciences
Lei Wang, Yan Liu, Xu Zhang, Yingze Ye, Xiaoxing Xiong, Shudi Zhang, Lijuan Gu, Zhihong Jian, Hongfa Wang
Summary: Ischemic stroke is a cerebrovascular disease that can lead to severe disability and death. Current treatment methods for ischemic stroke are limited and have a narrow treatment window. Recovery of cerebral blood flow causes cerebral ischemia/reperfusion injury, in which endoplasmic reticulum stress plays a crucial role.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Review
Plant Sciences
Yao Liu, Yonglun Lv, An Wei, Mujin Guo, Yanjie Li, Jiaojiao Wang, Xinhua Wang, Yan Bao
Summary: This article reviews the unfolded protein response (UPR), one of the systematic strategies used by eukaryotic cells to respond to endoplasmic reticulum (ER) stress. The UPR plays a crucial role not only in stress response, but also in plant growth and development.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Hematology
Alexander C. Lewis, Victoria S. Pope, Melinda N. Tea, Manjun Li, Gus O. Nwosu, Thao M. Nguyen, Craig T. Wallington-Beddoe, Paul A. B. Moretti, Dovile Anderson, Darren J. Creek, Maurizio Costabile, Saira R. Ali, Chloe A. L. Thompson-Peach, B. Kate Dredge, Andrew G. Bert, Gregory J. Goodall, Paul G. Ekert, Anna L. Brown, Richard D'Andrea, Nirmal Robinson, Melissa R. Pitman, Daniel Thomas, David M. Ross, Briony L. Gliddon, Jason A. Powell, Stuart M. Pitson
Summary: In this study, the accumulation of ceramide in AML cells induced an apoptotic integrated stress response through the activation of transcription factor ATF4. This response led to the degradation of the prosurvival protein Mcl-1, resulting in cell death. Combination treatment with the Bcl-2 inhibitor venetoclax synergistically killed AML cells and reduced leukemic stem cells.
Article
Hematology
Marco Busnelli, Stefano Manzini, Matteo Chiara, Alice Colombo, Fabrizio Fontana, Roberto Oleari, Francesco Poti, David Horner, Stefano Bellosta, Giulia Chiesa
Summary: The study found that overexpression of ApoA-I in EKO mice aorta modulates the development of atherosclerosis, affecting pathways beyond those associated with inflammation and immune response.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Review
Oncology
Monica Marzagalli, Fabrizio Fontana, Michela Raimondi, Patrizia Limonta
Summary: Cancer stem cells (CSCs) are a subset of cancer cells with tumor-initiating and self-renewal capacity, as well as high adaptive abilities, contributing to treatment failure and tumor progression/relapse. Understanding the molecular mechanisms associated with stemness-driven resistance is crucial for developing more effective drugs and durable responses. Explored mechanisms by CSCs to overcome different therapeutic strategies highlight their plasticity as an insidious trait responsible for their adaptation/escape, with novel CSC-specific approaches showing promising preclinical and clinical applications.
Review
Oncology
Fabrizio Fontana, Emanuela Carollo, Genevieve E. Melling, David R. F. Carter
Summary: Extracellular vesicles play a crucial role in the development of cancer drug resistance, affecting tumor cells' sensitivity to treatment through various mechanisms. They have the potential to serve as diagnostic and therapeutic targets in cancer therapy.
Article
Biochemistry & Molecular Biology
Michela Raimondi, Fabrizio Fontana, Monica Marzagalli, Matteo Audano, Giangiacomo Beretta, Patrizia Procacci, Patrizia Sartori, Nico Mitro, Patrizia Limonta
Summary: The study demonstrates that delta-tocotrienol induces paraptotic cell death in human melanoma cells, causing endoplasmic reticulum dilation and mitochondrial swelling. These alterations lead to impaired mitochondrial function, ROS production, and calcium overload.
Review
Cell Biology
Fabrizio Fontana, Patrizia Limonta
Summary: Understanding the molecular mechanisms of prostate cancer progression to the castration-resistant stage is crucial for improving therapeutic options. The activation of the androgen/androgen receptor axis and the GnRH/GnRH-R axis in CRPC cells play significant roles in antitumor activity, suggesting potential therapeutic implications.
Article
Oncology
Chiara Vitale, Monica Marzagalli, Silvia Scaglione, Alessandra Dondero, Cristina Bottino, Roberta Castriconi
Summary: Immunotherapies are promising strategies for cancer treatment, but better preclinical tools are needed to predict individual patients' response to therapy. Reliable preclinical models that reproduce the tumor environment while overcoming the limitations of traditional systems are necessary. This review discusses the tumor immune responses, escape mechanisms, and the recent 3D biomaterial-based cancer in vitro models that can be used to study the effects of different immunotherapeutic approaches.
Article
Biochemical Research Methods
Ilaria Pulsoni, Markus Lubda, Maurizio Aiello, Arianna Fedi, Monica Marzagalli, Joerg von Hagen, Silvia Scaglione
Summary: In vitro diffusive models are important for evaluating the penetration ability of active ingredients in different formulations. This study compared the Franz Diffusion Cell with a novel fluid-dynamic platform and assessed the penetration ability of caffeine and LIP1. The results showed similar penetration kinetics in both diffusive systems and the fluid-dynamic platform showed better prediction for lipophilic molecules.
Editorial Material
Oncology
Fabrizio Fontana, Martina Anselmi, Patrizia Limonta
Article
Oncology
Martina Anselmi, Fabrizio Fontana, Monica Marzagalli, Nicoletta Gagliano, Michele Sommariva, Patrizia Limonta
Summary: In melanoma patients, poor prognosis often correlates with high presence of cancer-associated neutrophils, indicating that tumors can recruit these immune cells to specifically sustain their own development and progression. However, the role of cancer stem cells (CSCs) in this dialogue has not been elucidated yet. Our results revealed that melanoma SCs can reshape the immune microenvironment by triggering a pro-tumor N2 phenotype in neutrophils, which in turn are able to confer stemness properties to melanoma cells.
Article
Cell Biology
Fabrizio Fontana, Martina Anselmi, Emanuela Carollo, Patrizia Sartori, Patrizia Procacci, David Carter, Patrizia Limonta
Summary: EVs derived from adipocytes can influence the traits of PCa cells and reduce sensitivity to docetaxel, promoting tumor progression and aggressiveness. This EV-mediated crosstalk between adipocytes and PCa contributes to tumor evolution.
Article
Cell Biology
Riccardo Cristofani, Margherita Piccolella, Marina Montagnani Marelli, Barbara Tedesco, Angelo Poletti, Roberta Manuela Moretti
Summary: This study evaluated the role of HSPB8 in cell growth and migration of melanoma cell lines. The restoration of HSPB8 expression caused cell growth arrest and antimigratory effect in melanoma cell lines with low HSPB8 levels. It was also found that HSPB8 regulates the levels of the active prenylated form of NRAS, and its inhibition induces autophagy activation.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Marina Montagnani Marelli, Giangiacomo Beretta, Roberta Manuela Moretti
Summary: Prostate cancer is the fifth leading cause of cancer death in men. Chemotherapeutic agents primarily induce apoptosis in tumor cells, but drug resistance often occurs due to defects in apoptotic cellular responses. As an alternative approach, inducing non-apoptotic cell death, such as necroptosis, may prevent drug resistance. In this study, the involvement of necroptosis in the anticancer activity of delta-tocotrienol in prostate cancer cells (DU145 and PC3) was evaluated.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Fabrizio Fontana, Martina Anselmi, Patrizia Limonta
Summary: Mitochondria, organelles involved in tumorigenesis, undergo metabolic and structural dynamics in various types of cancer. Prostate cancer (PCa) cells exhibit distinct metabolic changes during their progression, from inefficient oxidative phosphorylation to the Warburg effect and back to a combination of both pathways. Mutations in mitochondrial genes and the androgen receptor axis play a crucial role in PCa cell metabolic reprogramming. This review focuses on the mitochondrial dynamics in PCa and their potential as therapeutic targets.
