Cortactin- a novel target of prolactin-activated JAK2 signaling
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University of Toledo / OhioLINK
2011
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ndltd-OhioLink-oai-etd.ohiolink.edu-toledo13100849262021-08-03T06:08:03Z Cortactin- a novel target of prolactin-activated JAK2 signaling Laghate, Sneha Deepak Cellular Biology prolactin cortactin JAK2 breast cancer metastases invasion tyrosyl phosphorylation invadopodia Prolactin(PRL), is a cytokine/peptide hormone important for mammary gland development and has also been implicated in mammary neoplasia. PRL signals mainly via the receptor associated tyrosine kinase JAK2. It is known that PRL acts as a chemoattractant for breast carcinoma cells. Yet, the role of PRL in breast cancer invasion is not very well studied. We hypothesize that cortactin, an actin binding protein is a novel target of PRL-activated JAK2 leading to enhanced migration and invasiveness of breast cancer cells. Cortactin is an actin nucleation promoting factor (NPF) and accompanies N-WASP in Arp2/3 complex mediated actin polymerization leading to formation of invasive cytoskeletal structures such as invadopodia and podosomes. Cortactin is overexpressed in several cancers owing to the amplification of the EMS1/cortactin gene. Tyrosyl phosphorylation of cortactin downstream of Src and Src family of kinases is well studied and is implicated in breast cancer invasiveness and metastases. In this study we have demonstrated that overexpressed constitutively active JAK2 tyrosyl phosphorylates overexpressed cortactin in non-invasive T47D breast cancer cells. PRL-activated endogenous JAK2 also stimulates tyrosyl phosphorylation of endogenous cortactin in a time and concentration- dependent manner in invasive TMX2-28 breast cancer cells. Cortactin is an invadopodia marker protein and enhances invadopodia formation through interaction with MMPs which leads to degradation of the extracellular matrix (ECM). We have established the gelatin-matrix degradation assay and demonstrated gelatin-matrix degradation by invasive MDA-MB-231 and TMX2-28 breast cancer cells. The current study focuses on cortactin tyrosyl phosphorylation by PRL-activated JAK2 as a step towards invasion and matrix degradation by breast cancer cells. 2011-11-02 English text University of Toledo / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=toledo1310084926 http://rave.ohiolink.edu/etdc/view?acc_num=toledo1310084926 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Cellular Biology prolactin cortactin JAK2 breast cancer metastases invasion tyrosyl phosphorylation invadopodia |
| spellingShingle |
Cellular Biology prolactin cortactin JAK2 breast cancer metastases invasion tyrosyl phosphorylation invadopodia Laghate, Sneha Deepak Cortactin- a novel target of prolactin-activated JAK2 signaling |
| author |
Laghate, Sneha Deepak |
| author_facet |
Laghate, Sneha Deepak |
| author_sort |
Laghate, Sneha Deepak |
| title |
Cortactin- a novel target of prolactin-activated JAK2 signaling |
| title_short |
Cortactin- a novel target of prolactin-activated JAK2 signaling |
| title_full |
Cortactin- a novel target of prolactin-activated JAK2 signaling |
| title_fullStr |
Cortactin- a novel target of prolactin-activated JAK2 signaling |
| title_full_unstemmed |
Cortactin- a novel target of prolactin-activated JAK2 signaling |
| title_sort |
cortactin- a novel target of prolactin-activated jak2 signaling |
| publisher |
University of Toledo / OhioLINK |
| publishDate |
2011 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=toledo1310084926 |
| work_keys_str_mv |
AT laghatesnehadeepak cortactinanoveltargetofprolactinactivatedjak2signaling |
| _version_ |
1719431444974010368 |