Background: Calcium-mediated proteolysis plays an important role in cell migration. Lysophosphatidic acid (LPA), a lipid mediator present in serum, enhances migration of carcinoma cells. The effects of LPA on calpain-mediated proteolysis were, therefore, examined in PC-3, a human prostate cancer cell line.
Methods: Cultured PC-3 cells were used in studies utilizing pharmacologic interventions, immunoblotting, and confocal immunolocalization.
Results: Focal adhesion kinase (FAK), a tyrosine kinase involved in cell adhesion, is rapidly proteolyzed in serum-starved PC-3 cells exposed to the calcium ionophore, ionomycin; Nck, p130CAS, PKCα, and Ras-GAP are also degraded. Thapsigargin, which causes more moderate increases in intracellular calcium, induces partial proteolysis of these proteins. Calpain inhibitors block the proteolytic responses to ionomycin and thapsigargin. Ionomycin does not induce proteolysis in cells maintained in serum, suggesting a protective role for growth factors contained in serum. LPA causes minor FAK proteolysis when added alone, but protects against ionomycin-induced proteolysis in a time-dependent manner. LPA also protects against the cell detachment that eventually follows ionomycin treatment. The response to LPA is blocked by an LPA receptor antagonist. A similar effect of LPA is observed in ionomycin-treated Rat-1 fibroblasts. In PC-3 cells, the protective effects of LPA and serum are correlated with phosphorylation and redistribution of paxillin, suggesting roles for phosphorylation-mediated protein-protein interactions.
Conclusions: The complex effects of LPA on calpain-mediated proteolysis of FAK and other adhesion proteins are likely to play a role in the ability of LPA to promote attachment, migration, and survival of prostate cancer cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/pros.22513 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Initiation of tumor dormancy by the lymphovascular embolus.
Oncotarget
October 2024
Department of Pathology, Anatomy and Cell Biology and the Clinical and Translational Research Center of Excellence, Meharry Medical College, Nashville, TN 37208, USA.
Article Synopsis
- Cancer dormancy and recurrence are linked to dormant micrometastasis which may originate from lymphovascular tumor emboli; the study explores if dormancy begins in these emboli.
- Experimental studies using a patient-derived xenograft of inflammatory breast cancer (Mary-X) reveal that during emboli formation, the cells show reduced proliferation and enter a dormant state due to specific molecular changes, including altered E-cadherin and mTOR signaling.
- Observational studies on human breast cancers confirm increased E-cadherin and decreased cell growth markers (Ki-67, mTOR) in lymphovascular tumor emboli, aligning with the experimental findings and highlighting a potential mechanism of dorm
Targeting calpain-2-mediated junctophilin-2 cleavage delays heart failure progression following myocardial infarction.
J Mol Cell Cardiol
September 2024
Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX, USA; Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA; Department of Medicine/Cardiology, Baylor College of Medicine, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Center for Space Medicine, Baylor College of Medicine, Houston, TX, USA. Electronic address:
Coronary heart disease (CHD) is a prevalent cardiac disease that causes over 370,000 deaths annually in the USA. In CHD, occlusion of a coronary artery causes ischemia of the cardiac muscle, which results in myocardial infarction (MI). Junctophilin-2 (JPH2) is a membrane protein that ensures efficient calcium handling and proper excitation-contraction coupling.
View Article and Find Full Text PDFNew perspective for Calpain-Mediated regulation of meat Quality: Unveiling the impact on mitochondrial pathway apoptosis in post-mortem.
Food Chem
May 2024
School of Food and Biological Engineering, Hefei University of Technology, Hefei 230601, China; Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, Hefei 230601, China. Electronic address:
While calpain's role in myofibrillar protein degradation is well-established, its impact on post-mortem apoptosis remains fully elucidated. This study aimed to examine how calpain influences the mitochondrial apoptotic pathway in post-mortem muscle cells and assess its potential impact on chicken tenderness. The findings indicate that the calpain inhibitor treatment could decelerate the rate of lysosome destruction in post-mortem chicken, which is a crucial factor in delaying the mitochondrial apoptotic pathway.
View Article and Find Full Text PDFMP Allosterically Activates AMPK to Enhance ABCA1 Stability by Retarding the Calpain-Mediated Degradation Pathway.
Int J Mol Sci
December 2023
State Key Laboratory for Bioactive Substances and Functions of Natural Medicines, Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Xian Nong Tan Street 1, Xicheng District, Beijing 100050, China.
It is widely recognized that macrophage cholesterol efflux mediated by the ATP-binding cassette transporter A1 (ABCA1) constitutes the initial and rate-limiting step of reverse cholesterol transport (RCT), displaying a negative correlation with the development of atherosclerosis. Although the transcriptional regulation of ABCA1 has been extensively studied in previous research, the impact of post-translational regulation on its expression remains to be elucidated. In this study, we report an AMP-activated protein kinase (AMPK) agonist called ((2R,3S,4R,5R)-3,4-dihydroxy-5-(6-((3-hydroxyphenyl) amino)-9H-purin-9-yl) tetrahydrofuran-2-yl) methyl dihydrogen phosphate (MP), which enhances ABCA1 expression through post-translational regulation rather than transcriptional regulation.
View Article and Find Full Text PDFCardiac ischemic preconditioning promotes cMyBP-C phosphorylation by inhibiting the calpain-mediated proteolysis.
Exp Cell Res
December 2023
State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, China; Department 5 of Cardiology, Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University, Urumqi, China. Electronic address:
Ischemic preconditioning (IPC) has been considered as the most important mean to protect against ischemia/reperfusion (I/R) induced heart injury. It has been reported that cardiac myosin binding protein-C (cMyBP-C) phosphorylation plays an essential role in cardiac protection against I/R-induced heart injury. However, it is still obscured whether IPC-mediated cardiac protection is causally related to cMyBP-C phosphorylation and proteolysis and, if so, what the underlying mechanism is.
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!