Accession Number : ADA594253


Title :   Role of Stat3 and ErbB2 in Breast Cancer


Descriptive Note : Annual summary rept. 15 Sep 2009-14 Sep 2013


Corporate Author : QUEEN'S UNIV KINGSTON (ONTARIO)


Personal Author(s) : Geletu, Mulu


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a594253.pdf


Report Date : Dec 2013


Pagination or Media Count : 103


Abstract : Stat3 (Signal Transducer and Activator of Transcription-3) is activated by a number of receptor and nonreceptor tyrosine kinases. We recently demonstrated that engagement of E-cadherin, a calcium-dependent, cell to cell adhesion molecule which is often required for cells to remain tightly associated within the epithelium, also activates Stat3. We now examined the effect of two other classical cadherins, cadherin-11 and N-cadherin, whose expression often correlates with the epithelial to mesenchymal transition occurring in metastasis of carcinoma cells, upon Stat3 phosphorylation and activity. Our results indicate that engagement of these two cadherins also, can trigger a dramatic surge in Stat3 activity. This activation occurs through upregulation of members of the IL6 family of cytokines, and it is necessary for cell survival, proliferation and migration. Interestingly, our results also demonstrate for the first time that, in sharp contrast to Stat3, the activity of Erk (Extracellular Signal Regulated kinase) was unaffected by cadherin-11 engagement. Further examination indicated that, although IL6 was able to activate Erk in sparsely growing cells, IL6 could not induce an increase in Erk activity levels in densely growing cultures. Most importantly, cadherin-11 knock-down did allow Erk activation by IL6 at high densities, indicating that it is indeed cadherin engagement that prevents Erk activation by IL6. The fact that the three classical cadherins tested so far, E-cadherin, N-cadherin and cadherin11, which are present in essentially all tissues, actually activate Stat3 regardless of their role in metastasis, argues for Stat3 as a central survival, rather than invasion factor.


Descriptors :   *BREAST CANCER , ACTIVATION , ADHESION , CANADA , CELLS(BIOLOGY) , CONTRAST , EPITHELIUM , INDICATORS , METASTASIS , MOLECULES , PHOSPHORUS TRANSFERASES , SURVIVABILITY , TISSUES(BIOLOGY) , TRANSDUCERS , TRANSITIONS , TRIGGER CIRCUITS , TYROSINE


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE