PUBLICATION
LAPTM4B-35 promotes cancer cell migration via stimulating integrin beta1 recycling and focal adhesion dynamics
- Authors
- Liu, M., Yan, R., Wang, J., Yao, Z., Fan, X., Zhou, K.
- ID
- ZDB-PUB-220406-5
- Date
- 2022
- Source
- Cancer science 113(6): 2022-2033 (Journal)
- Registered Authors
- Keywords
- Cdc42, Filopodia, Focal adhesion, Integrin beta1 recycling, LAPTM4B-35
- MeSH Terms
-
- Animals
- Cell Adhesion
- Cell Line, Tumor
- Cell Movement/physiology
- Focal Adhesions/metabolism
- Humans
- Integrin beta1*/metabolism
- Lysosomes/metabolism
- Membrane Proteins/metabolism
- Neoplasms*/metabolism
- Oncogene Proteins/metabolism
- Zebrafish/metabolism
- PubMed
- 35381120 Full text @ Cancer Sci.
Citation
Liu, M., Yan, R., Wang, J., Yao, Z., Fan, X., Zhou, K. (2022) LAPTM4B-35 promotes cancer cell migration via stimulating integrin beta1 recycling and focal adhesion dynamics. Cancer science. 113(6):2022-2033.
Abstract
Metastasis is the main cause of cancer patients' death despite tremendous efforts invested in developing the related molecular mechanisms. During cancer cell migration, cells undergo dynamic regulation of filopodia, focal adhesion, and endosome trafficking. Cdc42 is imperative for maintaining cell morphology and filopodia, regulating cell movement. Integrin beta1 activates on the endosome, the majority of which distributes itself on the plasma membrane, indicating that endocytic trafficking is essential for this activity. In cancers, high expression of Lysosome-Associated Protein Transmembrane 4B (LAPTM4B) is associated with poor prognosis. LAPTM4B-35 has been reported as displaying plasma-membrane distribution and being associated with cancer cell migration. However, the detailed mechanism of its isoform-specific distribution and whether it relates to cell migration remain unknown. Here we first report and quantify the filopodia localization of LAPTM4B-35: mechanically, that specific interaction with Cdc42 promoted its localization to the filopodia. Furthermore, our data show that LAPTM4B-35 stabilized filopodia, and regulated integrin beta1 recycling via interaction and co-trafficking on the endosome. In our zebrafish xenograft model, LAPTM4B-35 stimulated the formation and dynamics of focal adhesion, as well as further promoting cancer cell dissemination, whereas in skin-cancer patients, LAPTM4B level correlated with poor prognosis. In short, this study establishes an insight into the mechanism of LAPTM4B-35 filopodia distribution, as well as into its biological effects and its clinical significance, providing a novel target for cancer therapeutics development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping