| dc.identifier.uri | http://hdl.handle.net/11401/76487 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | Missing in Metastasis (MIM), also known as MTSS1, is a scaffold protein that is down-regulated in multiple metastatic cancer cell lines compared to non-metastatic counterparts. MIM regulates cytoskeletal dynamics and actin polymerization, and has been implicated in the control of cell motility and invasion. MIM has also been shown to bind to a receptor PTP, PTP-delta, an interaction that may provide a link between tyrosine phosphorylation-dependent signaling and metastasis. We used shRNA-mediated gene silencing to investigate the consequences of loss of MIM on the migration and invasion of the MCF10A mammary epithelial cell model of breast cancer. We observed that suppression of MIM by RNAi enhanced migration and invasion of MCF10A cells, effects that were mediated by enhancing the stability and quantity of PTP-delta. Furthermore, analysis of human clinical data indicated that PTP-delta was elevated in breast cancer samples when compared to normal tissue. We demonstrated that the SRC protein tyrosine kinase is a direct substrate of PTP-delta; and, upon suppression of MIM, we observed changes in the phosphorylation status of SRC, in particular the inhibitory site (Tyr 527) was hypophosphorylated, whereas the activating autophosphorylation site (Tyr 416) was hyperphosphorylated. Thus, the absence of MIM led to PTPdelta-mediated activation of SRC. Finally, the SRC inhibitor SU6656 counteracted the effects of MIM suppression on cell motility and invasion. This study illustrates that both SRC and PTP-delta may be considered therapeutic targets for metastatic tumors associated with loss of MIM. | |
| dcterms.available | 2017-09-20T16:50:24Z | |
| dcterms.contributor | Tonks, Nicholas K | en_US |
| dcterms.contributor | Carpino, Nicholas | en_US |
| dcterms.contributor | Miller, Todd | en_US |
| dcterms.contributor | VanAelst, Linda | en_US |
| dcterms.contributor | Lucito, Robert. | en_US |
| dcterms.creator | Chaudhary, Fauzia | |
| dcterms.dateAccepted | 2017-09-20T16:50:24Z | |
| dcterms.dateSubmitted | 2017-09-20T16:50:24Z | |
| dcterms.description | Department of Molecular and Cellular Biology. | en_US |
| dcterms.extent | 164 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.format | Application/PDF | en_US |
| dcterms.identifier | http://hdl.handle.net/11401/76487 | |
| dcterms.issued | 2014-12-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:50:24Z (GMT). No. of bitstreams: 1
Chaudhary_grad.sunysb_0771E_11791.pdf: 6099774 bytes, checksum: 798a245a7f26b1e5ac7100115e6b3b46 (MD5)
Previous issue date: 1 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Molecular biology | |
| dcterms.subject | Breast cancer, cell invasion, cell motility, Metastasis, Missing-in-metastasis, PTPdelta | |
| dcterms.title | Missing-in-Metastasis regulates cell motility and invasion via PTPδ mediated changes in SRC activity | |
| dcterms.type | Dissertation | |
