Signals from the epidermal growth factor (EGF) receptor and integrin-dependent adhesion to laminin contribute to the progression and metastasis of colonic tumors. However, little is know about the mechanisms by which these signals cooperate. Recently, we have reported that the colon cancer cell line LIM1215 secretes and adhere to autocrine laminin-10 via multiple integrin receptors and that EGF stimulates spreading of these cells on the same substrate. In this report, we investigate the effect of EGF and laminin-10 on colon cancer cell migration in vitro. EGF stimulates migration of LIM1215 cells in a wound healing assay. The response to EGF is inhibited by anti-EGF receptor antibody 528, the EGF receptor kinase inhibitor AG-1478, or the MAP kinase kinase inhibitor PD98059 but not the PI3-K inhibitor wortmannin. Using Transwell migration chambers, we demonstrate that laminin-10 but not collagen-I, collagen-IV, or a commercial preparation of human placental laminin is a potent motility factor for LIM1215 cells. The migration response to laminin-10 is increased upon stimulation of the cells with EGF and correlates with the up-regulation of alpha(6)beta(4) integrin expression as measured by analysis of Triton X-100-soluble cellular extracts. The results from integrin inhibition experiments indicate that basal migration on laminin-10 is mediated by alpha(3)beta(1) but not alpha(2)beta(1) nor alpha(6)beta(4) integrins. Alpha(3) blocking antibodies also inhibited EGF-stimulated chemokinetic migration of LIM1215 cells on laminin-10. However, in contrast to unstimulated cells, alpha(6) or beta(4) integrin-blocking antibodies inhibited the migration of EGF-stimulated cells by up to 50%. Taken together, these results support the cooperative role of EGF receptor and laminin-10 on colon cancer cell motility and suggest a critical role for both the alpha(3)beta(1) and the alpha(6)beta(4) integrins in this process.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1006/excr.2001.5197 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Alterations in the microenvironment of junctional epidermolysis bullosa keratinocytes: a gene expression study.
Matrix Biol
November 2024
Department of Dermatology, Medical Center - University of Freiburg, Freiburg, Germany. Electronic address:
Integrin α6β4 subunits and type XVII collagen are critical transmembrane proteins involved in cell-matrix adhesion in skin, while laminin 332 serves as their ligand in the basement membrane zone (BMZ). Those proteins contribute to the composition of hemidesmosomes (HDs) and pathogenic variants in their corresponding genes cause junctional epidermolysis bullosa (JEB). Although the genotype-phenotype relationships in JEB have been extensively studied, the pathogenetic changes of extracellular matrix (ECM) and cell-matrix adhesion resulting from gene mutations remain unclear.
View Article and Find Full Text PDFIntegrin mutations in blistering skin diseases and related genetically engineered mouse models.
Hum Immunol
November 2024
Department of Surgery Albany Medical College, Albany, NY 12208, USA; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA. Electronic address:
As major receptors for cellular adhesion, integrins in the epidermis are critical to maintain skin integrity. Integrins α6β4 and α3β1 are among the most highly and widely expressed integrins in the skin. Perhaps not surprisingly, mutation in subunits associated with these integrins cause variations of a blistering skin disease called junctional epidermolysis bullosa (JEB), which is characterized by blisters that form between the epidermis and dermis of the skin.
View Article and Find Full Text PDFIntegrin α6β4 Upregulates PTPRZ1 Through UCHL1-Mediated Hif-1α Nuclear Accumulation to Promote Triple-Negative Breast Cancer Cell Invasive Properties.
Cancers (Basel)
October 2024
Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA.
Integrin α6β4 drives triple-negative breast cancer (TNBC) aggressiveness through the transcriptional regulation of key genes. Here, we investigated how integrin α6β4 regulates protein tyrosine phosphatase receptor type Z1 (PTPRZ1). Using stable re-expression of integrin β4 (ITGB4) in cells naturally devoid of integrin α6β4 or knockdown or knockout (KO) of ITGB4, we found that integrin α6β4 regulates PTPRZ1 expression.
View Article and Find Full Text PDFBreast cancer-derived CAV1 promotes lung metastasis by regulating integrin α6β4 and the recruitment and polarization of tumor-associated neutrophils.
Int J Biol Sci
November 2024
The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang 330006, China.
Lung metastasis in breast cancer (BC) patients is one of the main reasons for their high mortality rate. The most prevalent BC small extracellular vesicles (sEVs receptor, integrin α6β4, has been found to interact with surfactant-associated protein (SFTPC) in lung epithelial cells, making BC more likely to metastasize to the lung. Tumor-associated neutrophils (TANs) play an essential role in BC lung metastasis as a component of the lung pre-metastatic niche (PMN) with two sides.
View Article and Find Full Text PDFFUT3 promotes gastric cancer cell migration by synthesizing Lea on ITGA6 and GLG1, affecting adhesion and vesicle distribution.
Life Sci
December 2024
Comprehensive Breast Care Center, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, PR China; Department of Cell Biology and Genetics, Center of Teaching and Experiment for Medical Post Graduates, School of Basic Medical Sciences, Biomedical Experimental Center, Xi'an Jiaotong University Health Science Center, Xi'an 710061, PR China. Electronic address:
Aims: Lewis antigen plays an important role in the progression of gastric cancer (GC), FUT3 is a key enzyme in the synthesis of Lewis antigen, but the molecular mechanism of its promotion of GC progression remains unclear.
Main Methods: We used Lea-antibody capturing coupled with mass spectrometry to identify the target proteins of FUT3, immunofluorescence (IF), molecular biology and cell function experiments were conducted to clarify the molecular mechanism of FUT3 promoting the migration and invasion of GC cells by regulating Lea glycosylation on ITGA6 and GLG1.
Key Findings: FUT3 promote migration and invasion of GC cells.
Want 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!