LAPTM4B-35 promotes cancer cell migration via stimulating integrin beta1 recycling and focal adhesion dynamics

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http://hdl.handle.net/10138/346118

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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 , vol. 113 , no. 6 , pp. 2022-2033 . https://doi.org/10.1111/cas.15362

Title: LAPTM4B-35 promotes cancer cell migration via stimulating integrin beta1 recycling and focal adhesion dynamics
Author: Liu, Minxia; Yan, Ruyu; Wang, Junjie; Yao, Zhihong; Fan, Xinyu; Zhou, Kecheng
Contributor organization: Institute for Molecular Medicine Finland
Helsinki Institute of Life Science HiLIFE
Department of Anatomy
University of Helsinki
Date: 2022-06
Language: eng
Number of pages: 12
Belongs to series: Cancer Science
ISSN: 1347-9032
DOI: https://doi.org/10.1111/cas.15362
URI: http://hdl.handle.net/10138/346118
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 cotrafficking on the endosome. In our zebrafish xenograft model, LAPTM4B-35 stimulated the formation and dynamics of focal adhesion, 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.
Subject: Cdc42
filopodia
focal adhesion
integrin beta1 recycling
LAPTM4B-35
FILOPODIA
PROTEIN
METASTASIS
GROWTH
CDC42
ENDOCYTOSIS
RESISTANCE
TUMORS
3122 Cancers
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion


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