The CD9/CD81 tetraspanin complex and tetraspanin CD151 regulate ?3?1 integrin-dependent tumor cell behaviors by overlapping but distinct mechanisms.
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ABSTRACT: Integrin ?3?1 potently promotes cell motility on its ligands, laminin-332 and laminin-511, and this may help to explain why ?3?1 has repeatedly been linked to breast carcinoma progression and metastasis. The pro-migratory functions of ?3?1 depend strongly on lateral interactions with cell surface tetraspanin proteins. Tetraspanin CD151 interacts directly with the ?3 integrin subunit and links ?3?1 integrin to other tetraspanins, including CD9 and CD81. Loss of CD151 disrupts ?3?1 association with other tetraspanins and impairs ?3?1-dependent motility. However, the extent to which tetraspanins other than CD151 are required for specific ?3?1 functions is unclear. To begin to clarify which aspects of ?3?1 function require which tetraspanins, we created breast carcinoma cells depleted of both CD9 and CD81 by RNA interference. Silencing both of these closely related tetraspanins was required to uncover their contributions to ?3?1 function. We then directly compared our CD9/CD81-silenced cells to CD151-silenced cells. Both CD9/CD81-silenced cells and CD151-silenced cells showed delayed ?3?1-dependent cell spreading on laminin-332. Surprisingly, however, once fully spread, CD9/CD81-silenced cells, but not CD151-silenced cells, displayed impaired ?3?1-dependent directed motility and altered front-rear cell morphology. Also unexpectedly, the CD9/CD81 complex, but not CD151, was required to promote ?3?1 association with PKC? in breast carcinoma cells, and a PKC inhibitor mimicked aspects of the CD9/CD81-silenced cell motility defect. Our data reveal overlapping, but surprisingly distinct contributions of specific tetraspanins to ?3?1 integrin function. Importantly, some of CD9/CD81's ?3?1 regulatory functions may not require CD9/CD81 to be physically linked to ?3?1 by CD151.
SUBMITTER: Gustafson-Wagner E
PROVIDER: S-EPMC3629153 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
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