Tumor cell migration depends on the interactions of adhesion proteins with the extracellular matrix. Lutheran/basal cell adhesion molecule (Lu/BCAM) promotes tumor cell migration by binding to laminin α5 chain, a subunit of laminins 511 and 521. Lu/BCAM is a type I transmembrane protein with a cytoplasmic domain of 59 (Lu) or 19 (Lu(v13)) amino acids. Here, using an array of techniques, including site-directed mutagenesis, immunoblotting, FRET, and proximity-ligation assays, we show that both Lu and Lu(v13) form homodimers at the cell surface of epithelial cancer cells. We mapped two small--small motifs in the transmembrane domain as potential sites for monomers docking and identified three cysteines in the cytoplasmic domain as being critical for covalently stabilizing dimers. We further found that Lu dimerization and phosphorylation of its cytoplasmic domain were concomitantly needed to promote cell migration. We conclude that Lu is the critical isoform supporting tumor cell migration on laminin 521 and that the Lu:Lu(v13) ratio at the cell surface may control the balance between cellular firm adhesion and migration.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791331 | PMC |
| http://dx.doi.org/10.1074/jbc.RA119.007521 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Molecular Mechanisms of circKIF4A in Breast Cancer Progression.
Asia Pac J Clin Oncol
January 2025
Department of Thyroid and Breast Surgery, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Aim: Breast cancer (BC) is the most frequently diagnosed malignancy worldwide, necessitating continued research into its molecular mechanisms. Circular RNAs (circRNAs) are increasingly recognized for their role in various cancers, including BC. This study explores the role of circRNA kinesin family member 4A (circKIF4A) in BC progression and its underlying molecular mechanisms.
View Article and Find Full Text PDFExpression of the IGF‑1Ea isoform in human placentas from third trimester normal and idiopathic intrauterine growth restriction singleton pregnancies: Correlations with clinical and histopathological parameters.
Mol Med Rep
March 2025
Department of Pathology, Aretaieion University Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece.
Intrauterine growth restriction (IUGR) is the second most common obstetric complication after preterm labor. Appropriate trophoblast differentiation and placental structure, growth and function are key for the maintenance of pregnancy and normal fetal growth, development and survival. Extravillous trophoblast cell proliferation, migration and invasion are regulated by molecules produced by the fetomaternal interface, including autocrine factors produced by the trophoblast, such as insulin‑like growth factor (IGF)‑1.
View Article and Find Full Text PDFRegulation of pancreatic cancer cells by suppressing KIN17 through the PI3K/AKT/mTOR signaling pathway.
Oncol Rep
February 2025
Department of Medical Laboratory, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, P.R. China.
Pancreatic cancer is an aggressive tumor, which is often associated with a poor clinical prognosis and resistance to conventional chemotherapy. Therefore, there is a need to identify new therapeutic markers for pancreatic cancer. Although KIN17 is a highly expressed DNA‑ and RNA‑binding protein in a number of types of human cancer, its role in pancreatic cancer development, especially in relation to progression, is currently unknown.
View Article and Find Full Text PDFIntegrated transcriptomics and proteomics analysis of the impact of iodine‑125 in hepatocellular carcinoma.
Mol Med Rep
March 2025
The First Central Clinical School, Tianjin Medical University, Tianjin 300000, P.R. China.
Hepatocellular carcinoma (HCC) is a common cause of cancer‑related mortality and morbidity worldwide. While iodine‑125 (I) particle brachytherapy has been extensively used in the clinical treatment of various types of cancer, the precise mechanism underlying its effectiveness in treating HCC remains unclear. In the present study, MHCC‑97H cells were treated with I, after which, cell viability and proliferation were assessed using Cell Counting Kit‑8, 5‑ethynyl‑2'‑deoxyuridine and colony formation assays, cell invasion and migration were evaluated using wound healing and Transwell assays, and cell apoptosis was determined using flow cytometry.
View Article and Find Full Text PDFKlotho attenuates epithelial‑mesenchymal transition of retinal pigment epithelial cells in subretinal fibrosis by suppressing the ERK1/2 and Wnt/β‑catenin signaling pathways.
Int J Mol Med
March 2025
Department of Ophthalmology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Retinal pigment epithelial (RPE) cells undergoing epithelial‑mesenchymal transition (EMT) are a key factor in promoting the progression of subretinal fibrosis. The klotho protein and gene exert anti‑fibrotic effects in multiple fibrotic diseases. However, the mechanisms involved in the role of klotho are unclear in subretinal fibrosis.
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!