Review
Immunology
Dandan Song, Yan Lian, Lin Zhang
Summary: AP-1 is a transcription factor involved in cell proliferation, migration, and invasion. Dysfunctional AP-1 activity is associated with cancer initiation, development, invasion, migration, and drug resistance. Small molecule inhibitors targeting AP-1 have shown some anticancer effects, but more research is needed to understand the specific mechanisms and select appropriate inhibitors and treatment strategies. Ultimately, this review summarizes the potential of combination therapy for cancer.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Neurosciences
Shuangquan Yu, Lingchao Chen, Kun Song, Ting Shu, Zheng Fang, Lujia Ding, Jilong Liu, Lei Jiang, Guanqing Zhang, Bing Zhang, Zhiyong Qin
Summary: This study investigated the regulatory mechanism of apoptosis and other forms of cell death in glioblastoma after irreversible electroporation (IRE), revealing the role of transcription factor AP-1 and its target gene Bim. The results also implicated three other forms of regulatory cell death (RCD): autophagy, necroptosis, and immunogenic cell death (ICD). IRE possibly mediates apoptosis through the AP-1-Bim pathway, causing mixed forms of RCD and potentially enhancing a systemic antitumor immune response.
Article
Biochemistry & Molecular Biology
Thomas Gabriel Mhone, Ming-Cheng Chen, Chia-Hua Kuo, Tzu-Ching Shih, Chung-Min Yeh, Tso-Fu Wang, Ray-Jade Chen, Yu-Chun Chang, Wei-Wen Kuo, Chih-Yang Huang
Summary: This study aimed to explore a tumor suppressive compound that can enhance the efficacy of Gefitinib treatment in lung cancer. Through in vitro and in vivo experiments, it was found that the combination of Daidzein and Gefitinib synergistically induced apoptosis and cell cycle arrest, effectively inhibiting lung cancer growth.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Medicine, Research & Experimental
Yuliu Zhang, Jianping Du, Xiaofan Duan, Wei Peng, Lei Lv, Zhiyu Chen, Yumei Zhang
Summary: In this study, RIPK1 expression was found to significantly contribute to cisplatin-induced apoptosis in human ESCC cells. Reduced RIPK1 expression promoted cell proliferation, while overexpressed RIPK1 facilitated apoptosis. Mechanistic investigations revealed that inhibition of RIPK1 proliferation in ESCC cells was regulated through activation of the c-Jun NH2-terminal kinase signaling pathway, leading to mitochondrial damage, ATP depletion, and increased reactive oxygen species generation.
Article
Biochemistry & Molecular Biology
Woo Yeon Hwang, Wook Ha Park, Dong Hoon Suh, Kidong Kim, Yong Beom Kim, Jae Hong No
Summary: DFMO significantly reduces cell viability in ovarian cancer cells through polyamine depletion and apoptosis pathways, as well as by mediating through AP-1, activating JNK, and enhancing the effect of cisplatin.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Taylor L. Wilson, Hyunjin Kim, Ching-Heng Chou, Deanna Langfitt, Robert C. Mettelman, Anastasia A. Minervina, E. Kaitlynn Allen, Jean-Yves Metals, Mikhail V. Pogorelyy, Janice M. Riberdy, M. Paulina Velasquez, Pratibha Kottapalli, Sanchit Trivedi, Scott R. Olsen, Timothy Lockey, Catherine Willis, Michael M. Meagher, Brandon M. Triplett, Aimee C. Talleur, Stephen Gottschalk, Jeremy Chase Crawford, Paul G. Thomas
Summary: By analyzing single-cell sequencing data, we identified unique effector precursor cells in preinfusion CAR T-cell products with higher functional potential and resistance to exhaustion.
Article
Pharmacology & Pharmacy
Huihui Wang, Chuangyu Wen, Siyu Chen, Weiqian Li, Qiyuan Qin, Lu He, Fang Wang, Junxiong Chen, Weibiao Ye, Wende Li, Junsheng Peng, Xiangling Yang, Huanliang Liu
Summary: The study demonstrates that chaetocin induces apoptosis in CRC cells by causing ROS accumulation and activating the JNK/c-Jun pathway, while also down-regulating CD47 expression and enhancing macrophages phagocytosis of CRC cells. Additionally, chaetocin inhibits tumor growth in CRC xenograft models, suggesting its potential as a candidate for CRC chemotherapy.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Yijing Ren, Cheng Lv, Jing Zhang, Beibei Zhang, Bei Yue, Xiaoping Luo, Zhilun Yu, Hao Wang, Junyu Ren, Zhengtao Wang, Wei Dou
Summary: Alantolactone (ATL) exhibits inhibitory effects on cell activities, induces apoptosis, and inhibits colony formation in colorectal cancer. It also reduces cell migration and invasion capabilities. Furthermore, ATL demonstrates significant anti-tumor effects in vivo models.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2021)
Article
Cell Biology
Michael Keith Kullmann, Fragka Pegka, Christian Ploner, Ludger Hengst
Summary: In addition to serving as a CDK inhibitor and tumor suppressor, p57 may also promote tumor growth by activating the proto-oncoprotein c-Jun.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
James T. Leech, Andrew Brennan, Nicola A. Don, Jody M. Mason, Neil M. Kad
Summary: The AP-1 transcription factor family plays a crucial role in regulating the cell cycle and has various functions in proliferation, differentiation, and stress response. This study shows that cFos can bind to DNA independently of cJun and can interact with DNA as both monomers and dimers.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Philipp Novoszel, Martin Holcmann, Gabriel Stulnig, Cristiano De Sa Fernandes, Victoria Zyulina, Izabela Borek, Markus Linder, Alexandra Bogusch, Barbara Drobits, Thomas Bauer, Carmen Tam-Amersdorfer, Patrick M. Brunner, Georg Stary, Latifa Bakiri, Erwin F. Wagner, Herbert Strobl, Maria Sibilia
Summary: This study found that c-Jun/AP-1 protein regulates CCL2 and IL-23 production in DCs following TLR7 activation, affecting psoriasis-like skin inflammation. The expression of CCL2 and IL-23 in human psoriatic skin co-localize with c-Jun in type-2/inflammatory DCs, and inhibition of JNK-AP-1 can reduce the expression of these targets in TLR7/8-stimulated human DCs.
EMBO MOLECULAR MEDICINE
(2021)
Article
Chemistry, Medicinal
Shenghan Gao, Xinyu Zhang, Jie Liu, Fuqing Ji, Zhihao Zhang, Qingjie Meng, Qi Zhang, Xiaogang Han, He Wu, Yulong Yin, Yonggang Lv, Wenzhen Shi
Summary: This study found that icariin (ICA) has an inhibitory effect on triple-negative breast cancer (TNBC) cells by inducing apoptosis and inhibiting cell invasion. The results suggest that ICA may be a potential drug for treating TNBC.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2023)
Article
Virology
Ruochan Han, Lin Liang, Tong Qin, Sa Xiao, Ruiying Liang
Summary: The 2A protein of encephalomyocarditis virus interacts with annexin A2 via the JNK/c-Jun pathway to inhibit apoptosis and promote viral proliferation. These findings contribute to our understanding of the molecular pathogenesis underlying EMCV infection.
Article
Oncology
Hao Li, Taoran Zhou, Yue Zhang, Hengyi Jiang, Jing Zhang, Zichun Hua
Summary: RuvBL1 is identified as a repressor of c-Jun/AP-1 activity leading to TRAIL resistance in lung cancer cells. Silencing RuvBL1 can sensitize resistant cells to TRAIL, while high expression of RuvBL1 inversely related to low c-Jun is associated with a poor overall prognosis in lung cancer patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Baowen Zhuo, Qifan Zhang, Tingyan Xie, Yidan Wang, Zhengliang Chen, Daming Zuo, Bo Guo
Summary: Regulatory T (Treg) cells in human tumors exhibit more potent immunosuppressive activity than peripheral blood Treg cells (PBTRs), which impairs the induction of effective antitumor immunity. This study explores the epigenetic profiles of tumor-infiltrating Treg cells (TITRs) and identifies functional regulatory elements. The researchers found global differences in chromatin accessibility and enhancer landscapes between TITRs and PBTRs, as well as two types of active enhancer formation in TITRs. They also discovered that the AP-1 family motifs are enriched at the enhancer regions of TITRs and validated the role of c-Jun in regulating signature genes of TITRs and Treg cell activation. The findings provide insights into the mechanism of AP-1-mediated activation of TITRs and may contribute to the development of new therapeutic strategies for liver cancer treatment.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Cell Biology
Carla Palma, Claudia La Rocca, Vincenzo Gigantino, Gabriella Aquino, Giovanni Piccaro, Dario Di Silvestre, Francesca Brambilla, Rossana Rossi, Fabrizia Bonacina, Maria Teresa Lepore, Matteo Audano, Nico Mitro, Gerardo Botti, Sara Bruzzaniti, Clorinda Fusco, Claudio Procaccini, Veronica De Rosa, Mario Galgani, Carlo Alviggi, Annibale Puca, Fabio Grassi, Tanja Rezzonico-Jost, Giuseppe Danilo Norata, Pierluigi Mauri, Mihai G. Netea, Paola de Candia, Giuseppe Matarese
Summary: The metabolic state is closely related to susceptibility to Mycobacterium tuberculosis infection, and controlled caloric restriction can reduce susceptibility to pulmonary MTB infection by inducing a metabolic shift and autophagy. This suggests that caloric restriction may be a feasible immunometabolic manipulation to control MTB infection and boost immunity against MTB.
Review
Biochemistry & Molecular Biology
Mario Galgani, Sara Bruzzaniti, Claudia La Rocca, Teresa Micillo, Paola de Candia, Maurizio Bifulco, Giuseppe Matarese
Summary: Regulatory T cells play a crucial role in suppressing pathological immune responses, but their enhanced suppressive capability in human cancers poses a major obstacle to anti-cancer immune responses. Research efforts have focused on understanding Treg cell biology, particularly the role of metabolism in ensuring Treg cell fitness in cancer. The unique biochemical characteristics of the tumor microenvironment support Treg cell metabolic activation, influencing their survival and proliferation. Targeting key metabolic pathways of tumor-resident Treg cells may represent the next frontier in cancer immunotherapy.
MOLECULAR ASPECTS OF MEDICINE
(2021)
Letter
Immunology
Francesco Perna, Sara Bruzzaniti, Erica Piemonte, Valeria Maddaloni, Lidia Atripaldi, Silvia Sale, Alessandro Sanduzzi, Carmine Nicastro, Nicola Pepe, Maurizio Bifulco, Giuseppe Matarese, Mario Galgani, Luigi Atripaldi
CLINICAL IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Silvia Garavelli, Francesco Prattichizzo, Antonio Ceriello, Mario Galgani, Paola de Candia
Summary: Type 1 diabetes is characterized by autoimmune destruction of insulin-secreting beta cells. Recent research suggests that extracellular vesicles (EVs) may serve as biomarkers and therapeutic targets for disease progression and complications.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Review
Oncology
Rosamaria Lappano, Lauren A. Todd, Mia Stanic, Qi Cai, Marcello Maggiolini, Francesco Marincola, Violena Pietrobon
Summary: Hormones and growth factors have significant effects on cellular processes and tumor growth, particularly in the context of hypoxia and hypoxia-inducible factors (HIFs). This review summarizes the current understanding of the role of hormones and growth factors in cancer development, with a focus on their interaction with hypoxia and HIFs. It also discusses how hypoxia influences the response to cancer immunotherapy, highlighting the potential impact of a hypoxic microenvironment on the success of adoptive cell therapies.
Article
Endocrinology & Metabolism
Sara Bruzzaniti, Erica Piemonte, Enza Mozzillo, Dario Bruzzese, Maria Teresa Lepore, Fortunata Carbone, Paola de Candia, Rocky Strollo, Antonio Porcellini, Marco Marigliano, Claudio Maffeis, Maurizio Bifulco, Johnny Ludvigsson, Adriana Franzese, Giuseppe Matarese, Mario Galgani
Summary: The levels of immune checkpoint molecules in the blood at the time of type 1 diabetes diagnosis were assessed, and their association with the risk of developing additional autoimmune disorders over time was determined.
Article
Biochemistry & Molecular Biology
Teresa Tropea, Damiano Rigiracciolo, Milena Esposito, Marcello Maggiolini, Maurizio Mandala
Summary: Increasing levels of estrogens in pregnancy contribute to the physiological adaptations of maternal vasculature. The GPER receptor plays a role in regulating uteroplacental blood flow through vasorelaxation in the uterine arteries. This study found that GPER expression and vasorelaxation are increased in pregnant rats compared to non-pregnant rats, suggesting the involvement of GPER in the regulation of uteroplacental blood flow during pregnancy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Ernestina Marianna De Francesco, Francesca Cirillo, Veronica Vella, Antonino Belfiore, Marcello Maggiolini, Rosamaria Lappano
Summary: Understanding the mechanisms of TNBC chemoresistance and exploring novel potential targets and methods for delivering chemotherapy are crucial for overcoming treatment hurdles and improving patient outcomes.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2022)
Article
Cell Biology
Maria Francesca Santolla, Marianna Talia, Francesca Cirillo, Domenica Scordamaglia, Salvatore De Rosis, Asia Spinelli, Anna Maria Miglietta, Bruno Nardo, Gianfranco Filippelli, Ernestina Marianna De Francesco, Antonino Belfiore, Rosamaria Lappano, Marcello Maggiolini
Summary: The AGEs/RAGE axis is involved in metabolic disorders and the dysfunctional interaction between breast cancer cells and tumor stroma. In this study, IL-8 was found to be the most up-regulated pro-inflammatory chemokine upon AGEs/RAGE activation in breast cancer-associated fibroblasts (CAFs). Furthermore, IL-8/CXCR1/2 paracrine activation induced migratory and invasive features in breast cancer cells. These findings highlight the importance of IL-8 in the AGEs/RAGE transduction pathway and its potential as a target for the management of breast cancer patients with metabolic disorders.
Article
Endocrinology & Metabolism
Rocky Strollo, Chiara Vinci, Y. K. Stella Man, Sara Bruzzaniti, Erica Piemonte, Ghadeer Alhamar, Silvia Irina Briganti, Ilaria Malandrucco, Flavia Tramontana, Chiara Fanali, James Garnett, Roberto Buccafusca, Perrin Guyer, Mark Mamula, Eddie A. James, Paolo Pozzilli, Johnny Ludvigsson, Paul G. Winyard, Mario Galgani, Ahuva Nissim
Summary: The study found that patients with type 1 diabetes had stronger antibody and T cell responses to insulin with oxidative post-translational modifications. Specific peptide segments induced stronger stimulation of CD4(+) and CD8(+) T cells in type 1 diabetes patients, leading to more antibody responses.
Article
Oncology
Cristina Pagano, Laura Coppola, Giovanna Navarra, Giorgio Avilia, Sara Bruzzaniti, Erica Piemonte, Mario Galgani, Rosa Della Monica, Lorenzo Chiariotti, Mariella Cuomo, Michela Buonaiuto, Giovanni Torelli, Pasquale Caiazzo, Chiara Laezza, Maurizio Bifulco
Summary: The study found that iPA treatment inhibits the translocation of EGFR to mitochondria and activates PUMA expression, leading to a change in cellular metabolism and induction of cell death. This has important implications for the treatment of glioblastoma.
Review
Biochemistry & Molecular Biology
Antonino Belfiore, Rosaria Valentina Rapicavoli, Rosario Le Moli, Rosamaria Lappano, Andrea Morrione, Ernestina Marianna De Francesco, Veronica Vella
Summary: Insulin-like growth factor 2 (IGF2) is upregulated in both childhood and adult malignancies and its overexpression is linked to chemotherapy resistance and poor prognosis. Dysregulation of IGF2 receptors and their downstream signaling effectors is involved in cancer initiation and progression. IGF2 plays a significant role in primary tumor development, cancer metastasis, immune evasion, and resistance to therapies, highlighting the need for further studies to identify therapeutic approaches targeting IGF2 action.
Editorial Material
Endocrinology & Metabolism
Sara Bruzzaniti, Erica Piemonte, Maria Teresa Lepore, Mario Galgani
DIABETES-METABOLISM RESEARCH AND REVIEWS
(2023)
Editorial Material
Cell Biology
Rosamaria Lappano, Marcello Maggiolini