Advances in biological regulation最新文献

{"title":"Conventional and alternative approaches for targeting PIK3CA and PTEN alterations in head and neck, breast, and other cancers","authors":"Jovanka Gencel-Augusto,&nbsp;Jennifer R. Grandis,&nbsp;Daniel E. Johnson","doi":"10.1016/j.jbior.2025.101117","DOIUrl":"10.1016/j.jbior.2025.101117","url":null,"abstract":"<div><div>Genetic alterations in genes encoding components of the PI3K/AKT/mTOR signaling pathway are frequently observed in head and neck squamous cell carcinoma (HNSCC), breast cancer, and a variety of other human malignancies. In particular, <em>PIK3CA</em>, encoding the p110α catalytic subunit of PI3K enzyme, is altered in approximately 30 % of HNSCC tumors and 37 % of breast cancer tumors. In addition, loss of PTEN protein, a negative regulator of PI3K signaling, occurs in roughly one-third of HNSCC. Here, we review the impact of these alterations on the growth and metabolism of cancer cells and summarize progress that has been made in the development and clinical evaluation of inhibitors that directly target p110α and related proteins. We also describe emerging approaches that are identifying unique vulnerabilities and targeting opportunities in tumors characterized by <em>PIK3CA</em> or <em>PTEN</em> alterations.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"99 ","pages":"Article 101117"},"PeriodicalIF":2.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The AP-4 accessory protein tepsin exhibits multivalent binding to LC3B","authors":"Cameron I. Cohen ,&nbsp;Amy K. Kendall ,&nbsp;Natalie S. Wallace ,&nbsp;Maggie L. McCorkle ,&nbsp;Lauren P. Jackson","doi":"10.1016/j.jbior.2025.101124","DOIUrl":"10.1016/j.jbior.2025.101124","url":null,"abstract":"<div><div>Tepsin is an accessory protein in Adaptor Protein 4 (AP-4) coated vesicles responsible for trafficking cargo from the <em>trans</em>-Golgi network (TGN). AP-4 vesicles recognize and sort multiple cargoes including ATG9A, a lipid scramblase essential for autophagosome maturation. In cultured cells, tepsin loss alters ATG9A distribution and autophagosome morphology, and tepsin has been shown to contain a canonical LC3-interacting region (LIR) motif required for proper ATG9A distribution. Computational modeling in AlphaFold Multimer combined with biochemical and biophysical experiments identified three additional LC3B binding motifs within tepsin disordered regions. Structural models paired with bio-layer interferometry (BLI) uncovered and confirmed specific residues involved in each interaction and indicated all four motifs independently engage the LC3B LIR docking site (LDS). Thermodynamic and kinetic properties associated with each motif found in full-length tepsin were quantified. BLI and biochemical data reveal all four motifs in tepsin must be mutated to abrogate binding to LC3B <em>in vitro</em>, while stoichiometry data estimate one tepsin likely binds two LC3B at one time on a surface or membrane. Together, data suggest tepsin could respond dynamically to LC3B concentrations on membranes by leveraging multivalency to modulate binding strength.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"99 ","pages":"Article 101124"},"PeriodicalIF":2.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the role of biomolecular condensates in cellular function and cancer","authors":"Herencia-Lagunar Elena ,&nbsp;Carrera-Bravo Claudia ,&nbsp;Castano Enrique ,&nbsp;Sztacho Martin","doi":"10.1016/j.jbior.2025.101105","DOIUrl":"10.1016/j.jbior.2025.101105","url":null,"abstract":"<div><div>Biomolecular condensates (BMCs) are membrane-less organelles formed through liquid-liquid phase separation, primarily driven by multivalent interactions between scaffold and client molecules. These dynamic compartments enable cells to spatially and temporally organize biochemical reactions by locally concentrating specific biomolecules, thereby enhancing the frequency of productive molecular interactions and increasing reaction rates. BMCs are integral to normal cellular physiology, with well-characterized examples including the nucleolus and Cajal bodies. However, aberrant formation or regulation of condensates has been implicated in the pathogenesis of several diseases, including neurodegenerative disorders, cancer, and immune-related conditions. Intrinsically disordered regions and disease-associated mutations in key residues often promote pathological phase separation, contributing to condensate dysregulation. A comprehensive understanding of the molecular principles governing BMC biogenesis is critical for the development of novel, non-invasive therapeutic strategies aimed at modulating condensate dynamics in disease contexts.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"98 ","pages":"Article 101105"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of glycolytic condensates in the cellular stress response during cancer progression","authors":"Elena Herencia-Lagunar,&nbsp;Claudia Carrera-Bravo,&nbsp;Martin Sztacho","doi":"10.1016/j.jbior.2025.101104","DOIUrl":"10.1016/j.jbior.2025.101104","url":null,"abstract":"<div><div>Biomolecular condensates are key organizers of the intracellular environment, which are formed through liquid–liquid phase separation. Glycolytic condensates constitute a subtype of biomolecular condensates that enable compartmentalized ATP production and efficient metabolite channeling under stress conditions. This review explores how stressors, such as hypoxia, glucose deprivation, hyperosmotic stress, and hyperthermia, induce the formation of glycolytic condensates. These stressors are notably prevalent in the tumor microenvironment, where they may support cancer cell survival, metabolic adaptation, and invasion. We discuss the role of scaffold molecules, such as TPM4, F-actin, and RNA, in mediating condensate assembly and stabilization. A deeper understanding of the regulation and function of glycolytic condensates could reveal new vulnerabilities in tumor metabolism and generate strategies to hinder cancer cell adaptation to stress.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"98 ","pages":"Article 101104"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144926143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA intercalating drugs: Mechanisms of action in cancer treatment","authors":"Marvellous Oyeyode ,&nbsp;Mathew Tempel ,&nbsp;Ted M. Lakowski ,&nbsp;James R. Davie","doi":"10.1016/j.jbior.2025.101115","DOIUrl":"10.1016/j.jbior.2025.101115","url":null,"abstract":"<div><div>DNA-intercalating drugs (e.g., doxorubicin) have been used in cancer treatment since the 1960s. Multiple mechanisms have been observed with these drugs. These drugs intercalate into nucleosome-free regions of chromatin, which play a crucial role in regulating gene expression and genome organization. DNA intercalation by these drugs results in a plethora of events, including DNA damage, chromatin damage (histone eviction), erosion of chromatin organization, nucleolar condensation, RNA polymerase I and/or RNA polymerase II degradation, transcription arrest, deubiquitination of histone H2B ubiquitinated at lysine 120, topoisomerase I and/or II inhibition and/or trapping, and disruption of proteins associated with the elongating RNA polymerase II. These events may occur within hours following the addition of these drugs. At later times, changes to the DNA structure (e.g., the formation of Z DNA) occur, and eventually, the cells will die via apoptosis. This review will examine the mechanisms of action of DNA-intercalating drugs, specifically two anthracyclines (doxorubicin and aclarubicin) and a heteroaromatic compound (BMH-21). Doxorubicin and aclarubicin are used clinically to treat cancer, while BMH-21 remains in preclinical development. Reports on plasma pharmacokinetics of these anthracyclines will be tabulated, and the clinical relevance of the observed mechanisms of action for doxorubicin and aclarubicin will be assessed based on this information.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"98 ","pages":"Article 101115"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuous fractionated irradiation with irradiation-free intervals enhances survival and clonogenicity in osteosarcoma MG-63 cells via adaptive DNA damage response","authors":"Hiroko Ikeda ,&nbsp;Yuka Amano ,&nbsp;Koki Hara ,&nbsp;Yuito Tanaka ,&nbsp;Eiki Isa ,&nbsp;Nanami Shimomura ,&nbsp;Toshifumi Tsujiuchi","doi":"10.1016/j.jbior.2025.101114","DOIUrl":"10.1016/j.jbior.2025.101114","url":null,"abstract":"<div><div>Radiotherapy is a widely used treatment modality for various types of cancer. However, the adaptive resistance of tumor cells during radiotherapy poses a major challenge to therapeutic efficacy. This study aimed to evaluate whether continuous fractionated irradiation induces radioresistance in osteosarcoma MG-63 cells compared with single-dose exposure. To assess the effects of fractionated irradiation on cell survival, MG-63 cells were subjected to either single irradiation (SR; 0, 5, or 10 Gy) or continuous fractionated irradiation (5-CFR; 0, 1, or 2 Gy per day for five consecutive days), resulting in total doses of 0, 5, or 10 Gy, respectively. Compared with SR, 5-CFR significantly increased survival and promoted the formation of larger colonies, indicating enhanced clonogenicity. We further examined the effects of additional irradiation (AR) following 5-CFR and an irradiation-free interval. Cells pretreated with 5-CFR (0, 1, or 2 Gy) were subsequently exposed to a single dose of AR (2 Gy), resulting in total doses of 0, 7, or 12 Gy, respectively. MG-63 cells that received 5-CFR + AR exhibited significantly greater survival and increased colony size compared to those treated with SR + AR. To explore the cellular response to DNA damage following 5-CFR, we analyzed γ-H2AX and 53BP1 foci formation. Both markers increased in a dose-dependent manner after 5-CFR, suggesting effective recognition and repair of DNA double-strand breaks. Collectively, these results indicate that continuous fractionated irradiation with irradiation-free intervals confers greater radioresistance to MG-63 cells by enhancing survival and clonogenicity via an adaptive DNA damage response compared with SR.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"98 ","pages":"Article 101114"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-depth review of breast cancer and inflammation pre-and post-treatment strategies with conventional and novel Steroid agents","authors":"Panneerselvam Theivendren ,&nbsp;Punitha Narayanasamy ,&nbsp;Kumarappan Chidamabaram ,&nbsp;Sangeetha Menon ,&nbsp;Josephin Arockia Dhivya Antony Sahayaraj ,&nbsp;Natarajan Kiruthiga ,&nbsp;Balaji Pandiyan","doi":"10.1016/j.jbior.2025.101102","DOIUrl":"10.1016/j.jbior.2025.101102","url":null,"abstract":"<div><div>Breast cancer leads to many women's cancer deaths worldwide and inflammation is essential for tumors to develop, advance and spread within the body. High levels of ongoing inflammation within the tumor help cancer cells multiply, encourage blood vessel formation and allow the cancer cells to evade detection by the immune system, so it is a target of choice for many cancer treatments. The relationship between breast cancer and inflammation is explored, stressing how important both early and late stages are, with both traditional and novel steroid options. For many years, corticosteroids and other conventional steroids have been used to help relieve side effects of treatment and boost the well-being of patients. Even so, steroids only working in certain patients and side effects have pushed scientists to discover new type of steroid derivatives that are better and safer. Targeted inflammation control and altered immune response in tumors by these new steroids could make therapy more successful. This review looks at current evidence from different types of studies to determine steroids' role in treating breast cancer-related inflammation. It also reviews options for using steroids together with chemotherapy, radiotherapy and immunotherapy, focusing on achieving the best anti-inflammatory results while keeping the inability to respond to treatment low. The study also looks at potential future progress in developing steroids, personalized medicine and therapies guided by biomarkers that could greatly improve how breast cancer is managed. Knowing how steroids affect tumors as well as inflammation is necessary for creating good treatment plans that improve breast cancer patients' chances of survival and lower their risk of disease recurrence.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"97 ","pages":"Article 101102"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Norepinephrine mediates adrenergic receptor transcription and oncogenic gene expression in pancreatic ductal adenocarcinoma","authors":"Henry H. Brak,&nbsp;Noelle R.J. Thielman","doi":"10.1016/j.jbior.2025.101097","DOIUrl":"10.1016/j.jbior.2025.101097","url":null,"abstract":"<div><div>Adrenergic stimulation of β₂ receptors has shown to increase pancreatic ductal adenocarcinoma (PDAC) proliferation and migration in an <em>in vitro</em> setting; however, the role of α₁ receptors in these adrenergic signaling pathways is unclear. Previous research has suggested that the MAPK signaling pathway is upregulated in response to β-adrenergic signaling, but other signaling pathways and downstream targets of mutant KRAS have yet to be investigated. This study investigates the role of adrenergic signaling through α₁ and β-receptors in two human-derived PDAC cell lines, examining proliferation, wound healing, and protein expression after treatment with norepinephrine (NE) and in the presence of β and α₁-receptor antagonism. Using RT-qPCR, the expression of adrenergic receptors and downstream KRAS effector proteins was evaluated. We found that NE has varying effects on proliferation and wound healing in different PDAC cell lines. Moreover, adrenergic receptor expression is under negative feedback control through α₁ signaling in both cell lines. Furthermore, NE decreases expression of MMP9 while also affecting expression of VIM, CCND1, mTOR, and rhoA. We demonstrate genotype dependent effects of adrenergic stimulation on downstream molecular signaling pathways in PDAC that are important for oncogenicity. Based on our findings, genotypic characterization of cell signaling pathways in PDAC may aid further research in effective therapeutics for PDAC.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"97 ","pages":"Article 101097"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The wheat VIH2-3B, a functional PPIP5K controls the localization of fasciclin-like arabinogalactan protein","authors":"Anuj Shukla ,&nbsp;Reshma Gopal ,&nbsp;Riya Ghosh ,&nbsp;Ankur Chaudhuri ,&nbsp;Kanupriya Agrwal ,&nbsp;Rahul Tanwar ,&nbsp;Henning Jacob Jessen ,&nbsp;Debabrata Laha ,&nbsp;Ajay Kumar Pandey","doi":"10.1016/j.jbior.2025.101103","DOIUrl":"10.1016/j.jbior.2025.101103","url":null,"abstract":"<div><div>Inositol pyrophosphates (PP-InsPs) are important signalling molecules that participate in multiple physiological processes across a wide range of eukaryotes. Metabolic pathway kinases (VIP1/VIHs) leading to the production of PP-InsPs are now well characterized in yeast and plants. Previously, the wheat (<em>Triticum aestivum</em> L.) inositol pyrophosphate kinase (TaVIH2) was shown to encode a catalytic active kinase domain. Heterologous expression of TaVIH2 in <em>Arabidopsis thaliana</em> was shown to enhance drought tolerance by modulating the cell composition. In this study, we attempted to identify the interacting protein targets of wheat VIH2-3B using a yeast two-hybrid (Y2H) cDNA library screen, which led to the identification of 52 putative interactors that are primarily involved in cell wall-related functions. Notably, fasciclin-like arabinogalactan protein (FLA7), a glycosylphosphatidyl inositol (GPI)-anchored protein, emerged as the most frequently interacting partner. Further analysis using pulldown assays validated the interaction between TaVIH2-3B and TaFLA7 in vivo. Using the reporter fusion studies, we observed the localization of TaFLA7 to be a plasma membrane and this localization of the TaFLA7 was perturbed in the yeast vip1Δ strain. The expression of TaVIH2-3B bearing PPIP5K enzymatic activity in yeast mutants rescued the level of IP₈ and restore the localization of the TaFLA7 to the membrane. Expression analysis of TaFLA7 revealed a differential expression response to drought in wheat shoot tissues. TaFLA7 was also found to be highly expressed during grain development, particularly in the endosperm and seed coat during grain maturation. Taken together, these findings highlight the potential role of TaVIH2 in cell wall remodelling and stress response pathways, offering new insights into the functional roles of VIH proteins in plants.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"97 ","pages":"Article 101103"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular responses to low nutrient conditions via activation of lysophosphatidic acid (LPA) receptor signaling in gastric cancer cells","authors":"Narumi Yashiro,&nbsp;Miwa Takai,&nbsp;Mao Yamamoto,&nbsp;Yuka Kusumoto,&nbsp;Shion Nagano,&nbsp;Anri Taniguchi,&nbsp;Moemi Tamura,&nbsp;Toshifumi Tsujiuchi","doi":"10.1016/j.jbior.2024.101068","DOIUrl":"10.1016/j.jbior.2024.101068","url":null,"abstract":"<div><div>In the center of the solid tumor, abnormal vascular architecture impedes sufficient blood supply, leading to continuous hypoxia and nutrient deprivation for the tumor cells. Lysophosphatidic acid (LPA) receptor signaling is known to drive a range of malignant behaviors in cancer cells. This study aimed to explore the impact of LPA receptors on cellular functions in gastric cancer AGS cells cultured under low nutrient conditions. When AGS cells were cultured in media containing low glucose (2000 mg/L), low glutamine (1 mM), or low amino acids (50 % content), LPA receptor expression levels were significantly altered. The growth activity of AGS cells cultured in low glucose- and low amino acid-containing media was suppressed by LPA. Conversely, LPA increased the growth activity of AGS cells cultured in low glutamine-containing media. AGS cell motility increased under low glucose and low glutamine conditions, while low amino acid conditions decreased cell motility. Additionally, the viability of AGS cells in response to cisplatin (CDDP) was enhanced under low glucose, low glutamine, and low amino acid conditions. The motility and viability of AGS cells in response to CDDP were significantly increased by AM966 (LPA₁ antagonist), GRI-977143 (LPA₂ agonist) and (2S)-OMPT (LPA₃ agonist). These results suggest that LPA receptor signaling is significantly implicated in regulating malignant properties in AGS cells under low nutrient conditions.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"96 ","pages":"Article 101068"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}