Journal article
CD151 promotes α3β1 integrin-dependent organization of carcinoma cell junctions and restrains collective cell invasion
Cancer Biology & Therapy, Vol.16(11), pp.1626-1640
10/30/2015
DOI: 10.1080/15384047.2015.1095396
PMCID: PMC4846106
PMID: 26418968
Abstract
Integrins function in collective migration both as major receptors for extracellular matrix and by crosstalk to adherens junctions. Despite extensive research, important questions remain about how integrin signaling mechanisms are integrated into collective migration programs. Tetraspanins form cell surface complexes with a subset of integrins and thus are good candidates for regulating the balance of integrin functional inputs into cell-matrix and cell-cell interactions. For example, tetraspanin CD151 directly associates with α3β1 integrin in carcinoma cells and promotes rapid α3β1-dependent single cell motility, but CD151 also promotes organized adherens junctions and restrains collective carcinoma cell migration on 2D substrates. However, the individual roles of CD151s integrin partners in CD151s pro-junction activity in carcinoma cells were not well understood. Here we find that CD151 promotes organized carcinoma cell junctions via α3β1 integrin, by a mechanism that requires the a3b1 ligand, laminin-332. Loss of CD151 promotes collective 3D invasion and growth in vitro and in vivo, and the enhanced invasion of CD151-silenced cells is α3 integrin dependent, suggesting that CD151 can regulate the balance between α3β1s pro-junction and pro-migratory activities in collective invasion. An analysis of human cancer cases revealed that changes in CD151 expression can be linked to either better or worse clinical outcomes depending on context, including potentially divergent roles for CD151 in different subsets of breast cancer cases. Thus, the role of the CD151-α3β1 complex in carcinoma progression is context dependent, and may depend on the mode of tumor cell invasion.
Details
- Title: Subtitle
- CD151 promotes α3β1 integrin-dependent organization of carcinoma cell junctions and restrains collective cell invasion
- Creators
- Shannin C Zevian - Department of Biology; University of IowaJessica L Johnson - Department of Biology; University of IowaNicole E Winterwood - Department of Biology; University of IowaKatherine S Walters - Central Microscopy Research Facility, University of IowaMary E Herndon - Department of Biology; University of IowaMichael D Henry - Holden Comprehensive Cancer Center, University of IowaChristopher S Stipp - Holden Comprehensive Cancer Center, University of Iowa
- Resource Type
- Journal article
- Publication Details
- Cancer Biology & Therapy, Vol.16(11), pp.1626-1640
- Publisher
- Taylor & Francis
- DOI
- 10.1080/15384047.2015.1095396
- PMID
- 26418968
- PMCID
- PMC4846106
- ISSN
- 1538-4047
- eISSN
- 1555-8576
- Language
- English
- Date published
- 10/30/2015
- Academic Unit
- Molecular Physiology and Biophysics; Pathology; Biology; Radiation Oncology; Pharmacy Practice and Science; Urology
- Record Identifier
- 9983991997002771
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