It has been demonstrated that the third component of complement (C3)(1) and its peptides increase normal and tumour cell proliferation. However, the signal cascade responsible for this phenomenon is still unknown. In this study, we elucidate some of the mechanisms involved in the signalling of C3 stimulation of cell proliferation. We have first investigated the in and out traffic of C3 peptides, then we have identified the subcellular localisation of internalised C3 and, finally, we have explored the role of protein phosphorylation in C3 traffic and in the proliferation of the Lewis lung carcinoma (3LL) cells. Our results indicate that traffic of C3 is not dependent on cytoskeletal integrity and requires protein kinase C-dependent phosphorylation. In addition, proliferation of 3LL cells stimulated by C3 depends on both C3 internalisation and protein-kinase C phosphorylation.
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http://dx.doi.org/10.1002/jcb.20336 | DOI Listing |
Proc Natl Acad Sci U S A
February 2025
Department of Biological Sciences, College of Liberal Arts and Sciences, Wayne State University, Detroit, MI 48202.
The mammalian Hippo kinases, MST1 and MST2, regulate organ development and suppress tumor formation by balancing cell proliferation and death. In macrophages, inflammasomes detect molecular patterns from invading pathogens or damaged host cells and trigger programmed cell death. In addition to lytic pyroptosis, the signatures associated with apoptosis are induced by inflammasome activation, but how the inflammasomes coordinate different cell death processes remains unclear.
View Article and Find Full Text PDFCirc Res
January 2025
Division of Cardiovascular Medicine, Department of Medicine (J.B.H., J.D.B., A.C.D.), Vanderbilt University Medical Center, Nashville, TN.
Cardiovascular and cardiometabolic diseases are leading causes of morbidity and mortality worldwide, driven in part by chronic inflammation. Emerging research suggests that the bone marrow microenvironment, or marrow niche, plays a critical role in both immune system regulation and disease progression. The bone marrow niche is essential for maintaining hematopoietic stem cells (HSCs) and orchestrating hematopoiesis.
View Article and Find Full Text PDFPLoS One
January 2025
Cell Therapy Center, The University of Jordan, Amman, Jordan.
Background: Hypoxia in tumor cells is linked to increased drug resistance and more aggressive behavior. In pancreatic cancer, the tumor microenvironment is notably hypoxic and exhibits strong immunosuppressive properties. Given that immunotherapy is now approved for pancreatic cancer treatment, further understanding of how pancreatic tumor cell hypoxia influences T-cell cytotoxicityis essential.
View Article and Find Full Text PDFJCI Insight
January 2025
Medical Oncology Department, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, Netherlands.
Background: Previously, we demonstrated that changes in circulating tumor DNA (ctDNA) are promising biomarkers for early response prediction (ERP) to immune checkpoint inhibitors (ICI) in metastatic urothelial cancer (mUC). In this study, we investigated the value of whole blood immunotranscriptomics for ERP-ICI and integrated both biomarkers into a multimodal model to boost accuracy.
Methods: Blood samples of 93 patients were collected at baseline and after 2-6 weeks of ICI for ctDNA (N=88) and immunotranscriptome (N=79) analyses.
Adv Biotechnol (Singap)
July 2024
MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, Guangdong, China.
Cellular plasticity, the remarkable adaptability of cancer cells to survive under various stress conditions, is a fundamental hallmark that significantly contributes to treatment resistance, tumor metastasis, and disease recurrence. Oncogenes, the driver genes that promote uncontrolled cell proliferation, have long been recognized as key drivers of cellular transformation and tumorigenesis. Paradoxically, accumulating evidence demonstrates that targeting certain oncogenes to inhibit tumor cell proliferation can unexpectedly induce processes like epithelial-to-mesenchymal transition (EMT), conferring enhanced invasive and metastatic capabilities.
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