Journal article
Transmembrane interactions are needed for KAI1/CD82-mediated suppression of cancer invasion and metastasis
The American journal of pathology, Vol.174(2), pp.647-660
02/2009
DOI: 10.2353/ajpath.2009.080685
PMCID: PMC2630572
PMID: 19116362
Abstract
In transmembrane (TM) domains, tetraspanin KAI1/CD82 contains an Asn, a Gln, and a Glu polar residue. A mutation of all three polar residues largely disrupts the migration-, invasion-, and metastasis-suppressive activities of KAI1/CD82. Notably, KAI1/CD82 inhibits the formation of microprotrusions and the release of microvesicles, while the mutation disrupts these inhibitions, revealing the connections of microprotrusion and microvesicle to KAI1/CD82 function. The TM polar residues are needed for proper interactions between KAI1/CD82 and tetraspanins CD9 and CD151, which also regulate cell movement, but not for the association between KAI1/CD82 and alpha3beta1 integrin. However, KAI1/CD82 still efficiently inhibits cell migration when either CD9 or CD151 is absent. Hence, KAI1/CD82 interacts with tetraspanin and integrin by different mechanisms and is unlikely to inhibit cell migration through its associated proteins. Moreover, without significantly affecting the glycosylation, homodimerization, and global folding of KAI1/CD82, the TM interactions maintain the conformational stability of KAI1/CD82, evidenced by the facts that the mutant is more sensitive to denaturation and less associable with tetraspanins and supported by the modeling analysis. Thus, the TM interactions mediated by these polar residues determine a conformation either in or near the tightly packed TM region and this conformation and/or its change are needed for the intrinsic activity of KAI1/CD82. In contrast to immense efforts to block the signaling of cancer progression, the perturbation of TM interactions may open a new avenue to prevent cancer invasion and metastasis.
Details
- Title: Subtitle
- Transmembrane interactions are needed for KAI1/CD82-mediated suppression of cancer invasion and metastasis
- Creators
- Rafijul Bari - Vascular Biology Center, University of Tennessee Health Science Center, Memphis, TN 38163, USAYanhui H Zhang - University of Tennessee Health Science CenterFeng ZhangNick X WangChristopher S StippJie J ZhengXin A Zhang
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.174(2), pp.647-660
- Publisher
- United States
- DOI
- 10.2353/ajpath.2009.080685
- PMID
- 19116362
- PMCID
- PMC2630572
- ISSN
- 1525-2191
- eISSN
- 1525-2191
- Grant note
- CA-96991 / NCI NIH HHS R01 GM069916 / NIGMS NIH HHS R01 GM069916-04 / NIGMS NIH HHS R01 CA096991 / NCI NIH HHS
- Language
- English
- Date published
- 02/2009
- Academic Unit
- Molecular Physiology and Biophysics; Biology
- Record Identifier
- 9983991962502771
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