Objectives: Pancreatic cancer is one of the most aggressive solid cancers and the fourth leading cause of cancer death in men and women. We previously showed that arginine depletion, using arginase I [HuArgI(Co)-PEG5000], selectively triggers cell death by autophagy in PANC-1 pancreatic cancer cells. The mechanism of action of [HuArgI(Co)-PEG5000], however, has remained poorly understood. In this study, we investigated the effects of arginine depletion on PANC-1 cell migration, adhesion, and invasion and determined the main molecular targets, which mediate PANC-1 cell response to treatment with HuArgI(Co)-PEG5000.
Methods: This was done through examining 2-dimensional (2D) cell motility assays (wound healing and time lapse), cell adhesion, and cell invasion assays, as well as immunostaining for focal adhesions and invadopodia in cells without or with the treatment with arginase.
Results: We demonstrate that arginine depletion decreases PANC-1 2D cell migration, adhesion, and 3D invasion. Moreover, our data suggest that these effects are mediated by autophagy and subsequent decrease in the activation of members of Ras homolog gene family (Rho) GTPase family.
Conclusions: Altogether, these findings uncover the mechanism of action of [HuArgI(Co)-PEG5000] and highlight the promising and selective anticancer potential for arginine depletion in the treatment of pancreatic cancer cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/MPA.0000000000001891 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Atg5 deficiency in basophils improves metabolism in lupus mice by regulating gut microbiota dysbiosis.
Cell Commun Signal
January 2025
Department of Nephrology, National Clinical Key Specialty Construction Program, Institute of Nephrology, Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Laboratory Medicine Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Autophagic activation in immune cells, gut microbiota dysbiosis, and metabolic abnormalities have been reported separately as characteristics of systemic lupus erythematosus (SLE). Elucidating the crosstalk among the immune system, commensal microbiota, and metabolites is crucial to understanding the pathogenesis of autoimmune diseases. Emerging evidence shows that basophil activation plays a critical role in the pathogenesis of SLE; however, the underlying mechanisms remain largely unknown.
View Article and Find Full Text PDFTargeting SRSF1 improves cancer immunotherapy by dually acting on CD8T and tumor cells.
Signal Transduct Target Ther
January 2025
Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
Serine arginine-rich splicing factor 1 (SRSF1) is a key oncogenic splicing factor in various cancers, promoting abnormal gene expression through post-translational regulation. Although the protumoral function of SRSF1 is well-established, the effects of inhibiting tumor-intrinsic SRSF1 on the tumor microenvironment and its impact on CD8 T cell-mediated antitumor immunity remain unclear. Our findings indicate that depleting SRSF1 in CD8 T cells improve antitumor immune function, glycolytic metabolism, and the efficacy of adoptive T cell therapy.
View Article and Find Full Text PDFDevelopment of a Genetically Encoded Sensor for Arginine.
ACS Sens
January 2025
School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
The amino acid l-arginine (Arg) plays important roles in multiple metabolic and physiological processes, and changes in its concentration have been implicated in pathological processes. While it is important to measure Arg levels in biological systems directly and in real-time, existing Arg sensors respond to l-ornithine or l-lysine. Here we report ArgS1, a new Arg sensor.
View Article and Find Full Text PDFExploring Integrin α5β1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights From Comprehensive Multicenter Preclinical Studies.
Circulation
January 2025
Pulmonary Hypertension Research Group, Québec Heart and Lung Institute Research Center, Quebec City, QC, Canada (S.-E.L., Y.G., T.Y., T.S., M.M., C.R., M.S., S.B.-B., A.B., C.T., A.P., R.E.K., S.M., K.Y., F.P., S.P., O.B., S.B.).
Background: Pulmonary arterial hypertension (PAH) is characterized by obliterative vascular remodeling of the small pulmonary arteries (PAs) and progressive increase in pulmonary vascular resistance leading to right ventricular failure. Although several drugs are approved for the treatment of PAH, mortality rates remain high. Accumulating evidence supports a pathological function of integrins in vessel remodeling, which are gaining renewed interest as drug targets.
View Article and Find Full Text PDFBioresponsive nanoreactor initiates cascade reactions for tumor vascular normalization and lactate depletion to augment immunotherapy.
Biomaterials
January 2025
School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, PR China. Electronic address:
Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment. However, abnormal tumor vasculature and excess lactate contribute to tumor immunosuppression and confer resistance to ICB therapy, seriously limiting its clinical application. Here, we have developed a bioresponsive nanoreactor, ALMn, which consists of hollow manganese dioxide nanoparticles with encapsulation of lactate oxidase and L-Arginine, to overcome immunosuppression and sensitize ICB therapy.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!