Tks5 and SHIP2 Regulate Invadopodium Maturation, but Not Initiation, in Breast Carcinoma Cells
Background: Tks5 regulates invadopodium formation, but the precise timing during invadopodium lifetime (initiation, stabilization, maturation) when Tks5 plays a role is not known. Results: We report new findings based on high-resolution spatiotemporal live-cell imaging of invadopodium precursor ass...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/110457 https://orcid.org/0000-0003-3214-4554 |
| _version_ | 1826191397965791232 |
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| author | Sharma, Ved P. Eddy, Robert Entenberg, David Condeelis, John Kai, Masayuki Gertler, Frank |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Sharma, Ved P. Eddy, Robert Entenberg, David Condeelis, John Kai, Masayuki Gertler, Frank |
| author_sort | Sharma, Ved P. |
| collection | MIT |
| description | Background: Tks5 regulates invadopodium formation, but the precise timing during invadopodium lifetime (initiation, stabilization, maturation) when Tks5 plays a role is not known.
Results: We report new findings based on high-resolution spatiotemporal live-cell imaging of invadopodium precursor assembly. Cortactin, N-WASP, cofilin, and actin arrive together to form the invadopodium precursor, followed by Tks5 recruitment. Tks5 is not required for precursor initiation but is needed for precursor stabilization, which requires the interaction of the phox homology (PX) domain of Tks5 with PI(3,4)P[subscript 2]. During precursor formation, PI(3,4)P[subscript 2] is uniformly distributed but subsequently starts accumulating at the precursor core 3–4 min after core initiation, and conversely, PI(3,4,5)P[subscript 3] gets enriched in a ring around the precursor core. SHIP2, a 5′-inositol phosphatase, localizes at the invadopodium core and regulates PI(3,4)P[subscript 2] levels locally at the invadopodium. The timing of SHIP2 arrival at the invadopodium precursor coincides with the onset of PI(3,4)P[subscript 2] accumulation. Consistent with its late arrival, we found that SHIP2 inhibition does not affect precursor formation but does cause decreases in mature invadopodia and matrix degradation, whereas SHIP2 overexpression increases matrix degradation.
Conclusions: Together, these findings lead us to propose a new sequential model that provides novel insights into molecular mechanisms underlying invadopodium precursor initiation, stabilization, and maturation into a functional invadopodium. |
| first_indexed | 2024-09-23T08:55:35Z |
| format | Article |
| id | mit-1721.1/110457 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:55:35Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1104572022-09-30T12:12:23Z Tks5 and SHIP2 Regulate Invadopodium Maturation, but Not Initiation, in Breast Carcinoma Cells Sharma, Ved P. Eddy, Robert Entenberg, David Condeelis, John Kai, Masayuki Gertler, Frank Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Kai, Masayuki Gertler, Frank Background: Tks5 regulates invadopodium formation, but the precise timing during invadopodium lifetime (initiation, stabilization, maturation) when Tks5 plays a role is not known. Results: We report new findings based on high-resolution spatiotemporal live-cell imaging of invadopodium precursor assembly. Cortactin, N-WASP, cofilin, and actin arrive together to form the invadopodium precursor, followed by Tks5 recruitment. Tks5 is not required for precursor initiation but is needed for precursor stabilization, which requires the interaction of the phox homology (PX) domain of Tks5 with PI(3,4)P[subscript 2]. During precursor formation, PI(3,4)P[subscript 2] is uniformly distributed but subsequently starts accumulating at the precursor core 3–4 min after core initiation, and conversely, PI(3,4,5)P[subscript 3] gets enriched in a ring around the precursor core. SHIP2, a 5′-inositol phosphatase, localizes at the invadopodium core and regulates PI(3,4)P[subscript 2] levels locally at the invadopodium. The timing of SHIP2 arrival at the invadopodium precursor coincides with the onset of PI(3,4)P[subscript 2] accumulation. Consistent with its late arrival, we found that SHIP2 inhibition does not affect precursor formation but does cause decreases in mature invadopodia and matrix degradation, whereas SHIP2 overexpression increases matrix degradation. Conclusions: Together, these findings lead us to propose a new sequential model that provides novel insights into molecular mechanisms underlying invadopodium precursor initiation, stabilization, and maturation into a functional invadopodium. National Institutes of Health (U.S.) (Grant CA150344) National Institutes of Health (U.S.) (Grant U54- CA112967) 2017-07-05T15:09:56Z 2017-07-05T15:09:56Z 2013-10 2013-07 Article http://purl.org/eprint/type/JournalArticle 0960-9822 1879-0445 http://hdl.handle.net/1721.1/110457 Sharma, Ved P. et al. “Tks5 and SHIP2 Regulate Invadopodium Maturation, but Not Initiation, in Breast Carcinoma Cells.” Current Biology 23.21 (2013): 2079–2089. https://orcid.org/0000-0003-3214-4554 en_US http://dx.doi.org/10.1016/j.cub.2013.08.044 Current Biology Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Sharma, Ved P. Eddy, Robert Entenberg, David Condeelis, John Kai, Masayuki Gertler, Frank Tks5 and SHIP2 Regulate Invadopodium Maturation, but Not Initiation, in Breast Carcinoma Cells |
| title | Tks5 and SHIP2 Regulate Invadopodium Maturation, but Not Initiation, in Breast Carcinoma Cells |
| title_full | Tks5 and SHIP2 Regulate Invadopodium Maturation, but Not Initiation, in Breast Carcinoma Cells |
| title_fullStr | Tks5 and SHIP2 Regulate Invadopodium Maturation, but Not Initiation, in Breast Carcinoma Cells |
| title_full_unstemmed | Tks5 and SHIP2 Regulate Invadopodium Maturation, but Not Initiation, in Breast Carcinoma Cells |
| title_short | Tks5 and SHIP2 Regulate Invadopodium Maturation, but Not Initiation, in Breast Carcinoma Cells |
| title_sort | tks5 and ship2 regulate invadopodium maturation but not initiation in breast carcinoma cells |
| url | http://hdl.handle.net/1721.1/110457 https://orcid.org/0000-0003-3214-4554 |
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