Review
Biochemistry & Molecular Biology
Sana Hibino, Tetsuro Kawazoe, Hidenori Kasahara, Shinji Itoh, Takatsugu Ishimoto, Mamiko Sakata-Yanagimoto, Koji Taniguchi
Summary: Inflammation plays a pivotal role in tumorigenesis and metastasis by suppressing anti-tumor immunity. Different types of tumors may have diverse responses to inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Rongqi Huang, Shuai Li, Chao Tian, Peng Zhou, Huifang Zhao, Wei Xie, Jie Xiao, Ling Wang, Jean de Dieu Habimana, Zuoxian Lin, Yuchen Yang, Na Cheng, Zhiyuan Li
Summary: The activation of TRPV2 has been found to promote cancerous behaviors and tumor formation and metastasis in ESCC cells. These effects are regulated by the HSP70/27 and PI3K/Akt/mTOR signaling pathways. TRPV2-PI3K/Akt/mTOR could be a promising target for the prevention and treatment of ESCC.
BRITISH JOURNAL OF CANCER
(2022)
Review
Biochemistry & Molecular Biology
Nana Zheng, Jiaqi Wei, Depei Wu, Yang Xu, Jianping Guo
Summary: PDK1 is a key protein kinase involved in regulating cell growth and cancer development, and it also modulates the tumor microenvironment and immunotherapies.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Review
Biochemistry & Molecular Biology
Nao Nagai, Yotaro Kudo, Daisuke Aki, Hayato Nakagawa, Koji Taniguchi
Summary: This article mainly discusses the effects of chronic inflammation on tumorigenesis and metastasis, as well as how it induces immune-suppressive tumor microenvironment. It also mentions the impact of chronic inflammation on age-related diseases, especially in the liver and colon.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Xin Lian, Kailin Yang, Renliang Li, Maomao Li, Jing Zuo, Bohao Zheng, Wei Wang, Ping Wang, Shengtao Zhou
Summary: Cellular metabolism plays a crucial role in cancer initiation and progression. While the metabolic alterations in cancer cells have been extensively studied, the metabolic states of immune cells in the tumor microenvironment (TME) are less well understood. This review focuses on the impact of oncometabolites on immune cell function and the clinical significance of targeting metabolism in anti-tumor immunotherapy. The metabolic changes in the immune system of TME provide novel therapeutic insights for cancer treatment.
Article
Oncology
Xuehui Jiang, Chaohui Wang, Ziliang Ke, Lina Duo, Ting Wu, Weihong Wang, Yong Yang, Yun Dai
Summary: TRPV1 plays an important role in regulating the immune microenvironment during colorectal tumorigenesis. Its hyperactivation promotes tumor initiation and progression by altering macrophage activation status and shifting the Th1/Th2 balance towards Th2 phenotype. Mechanistically, TRPV1 enhances M1 cytokine production in macrophages and activates the Calcineurin/NFATc2 signaling pathway to enhance Th2 immune response.
Article
Biochemistry & Molecular Biology
Chenming Ni, Wenyu Liu, Kailian Zheng, Shiwei Guo, Bin Song, Wei Jing, Gang Li, Bo Li, Canrong Ni, Keqing Shi, Gang Jin, Guanzhen Yu
Summary: The study discovered the presence of the MLL-AFF4 fusion gene in acute leukemia and investigated the role of AFF4 in pancreatic tumorigenesis. The results showed that overexpression of AFF4 promoted cell proliferation and cell cycle progression, while two nucleotide metabolism enzymes, HPRT1 and IMPDH2, were upregulated. The study also found that AFF4 was regulated by the PI3K/c-Myc axis and was positively correlated with c-Myc and HPRT1/IMPDH2 expression in clinical PDAC samples. These findings establish AFF4 as a potential biomarker and therapeutic target for PDAC.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Immunology
Jiayi Zang, Lin Xiao, Xin Shi, Sinan Liu, Yan Wang, Baolan Sun, Shaoqing Ju, Ming Cui, Rongrong Jing
Summary: Circular RNA plays a significant role in gastric cancer by regulating the expression of key molecules such as DEK and c-Myc, accelerating cancer development and metastasis, and affecting immune infiltration of CD8+ T cells.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Anatomy & Morphology
Yongbo Hu, Yiming He, Wei Liu, Shun Yu, Yabing Wei, Shaohua Bai, Yu Su, Bin Xiao
Summary: SIAH2 acts as an oncogene in colorectal cancer, promoting tumor proliferation, migration, and invasion. It activates the PI3K/AKT signaling pathway and is regulated by PTEN loss.
Article
Biochemistry & Molecular Biology
Wenxiu Liu, Hongyan Gou, Xiaohong Wang, Xiaoming Li, Xiaoxu Hu, Hao Su, Shengmian Li, Jun Yu
Summary: The study identified TTPAL as playing a crucial role in gastric cancer, promoting cancer cell proliferation, migration, and invasion through the PI3K/AKT signaling pathway, and may serve as a prognostic biomarker for GC patients.
Review
Cell Biology
Xiaodie Chen, Yunqing Li, Houjun Xia, Youhai H. Chen
Summary: Monocytes exhibit significant heterogeneity during homeostasis, inflammation, and tumorigenesis, which is influenced by tumor-induced microenvironmental changes. They play an important regulatory role in tumor development by affecting tumor growth or metastasis. Recent advances in single-cell technologies have provided a clear understanding of monocyte heterogeneity and subset-specific functions, allowing for systematic analysis of subset-specific roles in tumorigenesis. In this review, we discuss recent discoveries related to monocytes and tumorigenesis, as well as new strategies for tumor biomarker identification and anti-tumor immunotherapy.
Article
Multidisciplinary Sciences
Feng Zhi, Bowen Li, Chuanxia Zhang, Fan Xia, Rong Wang, Weihong Xie, Sihui Cai, Dawei Zhang, Ren Kong, Yiqiao Hu, Yilin Yang, Ya Peng, Jun Cui
Summary: NLRP6 enhances the PI3K/AKT pathway by binding and degrading p85 alpha, promoting tumorigenesis. The interaction between NLRP6 and p85 alpha offers a potential therapeutic target for tumor treatment.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Lei Wang, Zhiyu Fang, Peixiang Gao, Junfang Zheng
Summary: This study reveals a novel tumor-suppressing role of GLUD1 in ccRCC, providing new insights into inhibiting PI3K/Akt/mTOR activation and immune microenvironment.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Shunyao Zhu, Ziyi Luo, Xixi Li, Xi Han, Senlin Shi, Ting Zhang
Summary: Tumor-associated macrophages (TAMs) play a crucial role in the tumor microenvironment by secreting various factors that influence tumor growth and development. Different phenotypes of TAMs have distinct effects on tumors, making them an important target in tumor immunotherapy.
Review
Immunology
Eric Jou, Noe Rodriguez-Rodriguez, Andrew N. J. McKenzie
Summary: Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide, and current immunotherapeutic interventions have limited effectiveness. Cytokines interleukin-25 (IL-25) and IL-33, expressed by barrier epithelial cells, play important roles in the intestinal immune responses and can influence tumorigenesis in CRC. IL-25 and IL-33 have different effects on different subtypes of CRC and can modulate various immune cell types and pathways, including angiogenesis, tumor stemness, invasion, and metastasis.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Valentina Rausch, Valentina Sala, Fabio Penna, Paolo Ettore Porporato, Alessandra Ghigo
Summary: Cachexia is a severe complication of cancer characterized by progressive muscle and adipose tissue atrophy, resulting in weight loss, reduced quality of life, and shortened life expectancy. Cardiac muscle plays a significant role in cachexia, as cancer patients often experience cardiac abnormalities and heart failure symptoms. The lack of effective treatments underscores the need for further understanding of the underlying mechanisms, particularly the metabolic and proteolytic alterations in skeletal and cardiac muscles.
Review
Oncology
Michele Russo, Angela Della Sala, Carlo Gabriele Tocchetti, Paolo Ettore Porporato, Alessandra Ghigo
Summary: Heart failure is increasingly being recognized as a major complication of chemotherapy regimens, with doxorubicin (DOXO) remaining a commonly used but cardiotoxic anticancer agent. The molecular level effects of DOXO on the heart include mitochondrial dysfunction, DNA damage, and apoptosis. Dexrazoxane is currently the only FDA-approved cardioprotectant for patients treated with DOXO. However, research on the impact of DOXO on cardiac metabolism and potential pharmacological targets for prevention or treatment of DOXO cardiomyopathy is still ongoing.
CURRENT TREATMENT OPTIONS IN ONCOLOGY
(2021)
Article
Chemistry, Medicinal
Valentina Sala, Sophie Julie Cnudde, Alessandra Murabito, Alberto Massarotti, Emilio Hirsch, Alessandra Ghigo
Summary: Cystic fibrosis (CF) is a common rare genetic disease affecting over 70,000 people worldwide, characterized by lung blockage and chronic infections. Peptides hold promise as therapeutics for respiratory diseases like CF due to their high specificity, efficacy, and low toxicity, but face challenges like retention within mucus, proteolysis, immunogenicity, and aggregation in the development process. Solutions to overcome these issues and advancements in peptide design are being explored.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Gastroenterology & Hepatology
Andrea Costamagna, Dora Natalini, Maria del Pilar Camacho Leal, Matilde Simoni, Luca Gozzelino, Paola Cappello, Francesco Novelli, Chiara Ambrogio, Paola Defilippi, Emilia Turco, Elisa Giovannetti, Emilio Hirsch, Sara Cabodi, Miriam Martini
Summary: High expression of p130Cas is associated with higher histologic grade and poor prognosis in PDAC. Deletion of p130Cas inhibits acinar-derived tumorigenesis and progression by suppressing PI3K-AKT signaling. Targeting the PI3K pathway may be a rational therapeutic strategy for tumors with high expression of p130Cas.
Editorial Material
Cell Biology
Irene Franco, Gwladys Revechon, Maria Eriksson
Summary: The causal effects of somatic mutations in the aging process are still not clear due to technological and methodological weaknesses. Studying somatic mutagenesis in different experimental systems can help understand its functional role.
Article
Cell Biology
Alessandra Ghigo, Alessandra Murabito, Valentina Sala, Anna Rita Pisano, Serena Bertolini, Ambra Gianotti, Emanuela Caci, Alessio Montresor, Aiswarya Premchandar, Flora Pirozzi, Kai Ren, Angela Della Sala, Marco Mergiotti, Wito Richter, Eyleen de Poel, Michaela Matthey, Sara Caldrer, Rosa A. Cardone, Federica Civiletti, Andrea Costamagna, Nancy L. Quinney, Cosmin Butnarasu, Sonja Visentin, Maria Rosaria Ruggiero, Simona Baroni, Simonetta Geninatti Crich, Damien Ramel, Muriel Laffargue, Carlo G. Tocchetti, Renzo Levi, Marco Conti, Xiao-Yun Lu, Paola Melotti, Claudio Sorio, Virginia De Rose, Fabrizio Facchinetti, Vito Fanelli, Daniela Wenzel, Bernd K. Fleischmann, Marcus A. Mall, Jeffrey Beekman, Carlo Laudanna, Martina Gentzsch, Gergely L. Lukacs, Nicoletta Pedemonte, Emilio Hirsch
Summary: This study identifies PI3Kγ as a critical regulator of the cAMP signaling microdomain activated by β(2)-ARs. By using a PI3Kγ mimetic peptide (PI3Kγ MP) to displace the PKA pool anchored by PI3Kγ, cAMP can be safely increased in the lungs, leading to airway smooth muscle relaxation and reduced inflammation.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Jean Piero Margaria, Lucia Moretta, Jose Carlos Alves-Filho, Emilio Hirsch
Summary: This article summarizes the progress in understanding the role of PI3K/Akt in the development of lung fibrosis and its causative pathological context, including sepsis as well as acute lung injury (ALI) and its consequent acute respiratory distress syndrome (ARDS). Current knowledge about PI3K inhibitors for pulmonary fibrosis treatment, including drugs under development as well as in clinical trials, is further summarized. The discussion also includes how the design of inhaled compounds targeting the PI3K pathways might potentiate efficacy and improve tolerability.
Editorial Material
Cardiac & Cardiovascular Systems
Carlo G. Tocchetti, Alessandra Ghigo, Emilio Hirsch
Summary: This editorial discusses the study conducted by Lu et al. on the protective effect of circular RNA derived from the insulin receptor locus against doxorubicin-induced cardiotoxicity.
EUROPEAN HEART JOURNAL
(2022)
Editorial Material
Genetics & Heredity
Irene Franco, Maria Eriksson
Summary: With age, somatic mutations accumulate in the genome of healthy individuals, and recent sequencing data indicate a functional role for these mutations in aging and age-associated diseases.
NATURE REVIEWS GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Nicola Moro, Lolita Dokshokova, Induja Perumal Vanaja, Valentina Prando, Sophie Julie A. Cnudde, Anna Di Bona, Riccardo Bariani, Leonardo Schirone, Barbara Bauce, Annalisa Angelini, Sebastiano Sciarretta, Alessandra Ghigo, Marco Mongillo, Tania Zaglia
Summary: Doxorubicin is commonly used for cancer treatment, but its clinical use is limited by cardiotoxicity. Although the adverse cardiac effects of Doxorubicin are known, the underlying mechanisms are still not fully understood. Recent studies have found that Doxorubicin may not only affect cardiomyocytes but also cardiac sympathetic neurons, which are additional targets of Doxorubicin cardiotoxicity. These findings reveal a previously unrecognized effect of Doxorubicin on cardiac autonomic regulation, which plays a role in cardiac physiology and pathology, including heart failure and arrhythmias.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Respiratory System
Alessandra Ghigo, Chiara De Santi, Merrill Hart, Nilay Mitash, Agnieszka Swiatecka-Urban
Summary: CFTR is a regulated channel that is controlled by cAMP and PKA, and it is expressed on the luminal surface of epithelial cells involved in secretion and absorption. It plays a major role in the secretion of electrolytes activated by cAMP and Ca2+. CFTR secretes intracellular Cl- and bicarbonate and regulates the absorption of electrolytes by controlling the activity of ENaC in different tissues. The expression of CFTR gene is regulated by cell-specific and time-dependent mechanisms, and this review focuses on its transcriptional, post-transcriptional, and translational regulation in CF cells by cAMP-PKA, non-coding RNAs, and TGF-beta signaling pathways.
JOURNAL OF CYSTIC FIBROSIS
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Alessandra Ghigo, Pietro Ameri
CIRCULATION RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Antonietta Fazio, Camilla Evangelisti, Alessandra Cappellini, Sara Mongiorgi, Foteini-Dionysia Koufi, Irene Neri, Maria Vittoria Marvi, Michele Russo, Alessandra Ghigo, Lucia Manzoli, Roberta Fiume, Stefano Ratti
Summary: Phospholipase C (PLC) enzymes play a crucial role in the plasma membrane of mammalian cells, specifically in the cardiac sarcolemmal (SL) membrane of cardiomyocytes. They are responsible for hydrolyzing phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) into 1,2-diacylglycerol (DAG) and inositol (1,4,5) trisphosphate (Ins(1,4,5)P3), which are important lipid mediators. This review highlights the significance of PLC, particularly PLCβ isoforms, in the cardiovascular system, in both physiological and pathological conditions. Understanding the mechanisms of PLCβ activation and regulation holds promise for the development of therapeutic strategies for cardiac disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Alessandra Murabito, Janki Bhatt, Alessandra Ghigo
Summary: In the last fifteen years, the approval of the first molecular treatments has marked a breakthrough era for cystic fibrosis (CF) patients. The use of CFTR modulators has significantly improved lung function and quality of life for most CF patients. However, the efficacy of these drugs is still not optimal and the response varies among individuals with the same mutation. Therefore, there is a need to explore alternative approaches, such as modulating the cAMP signaling pathway, for therapeutic intervention in CF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
