Abstract 480: Psoriasin (S100A7) regulates epidermal growth factor signaling and actin polymerization in estrogen receptor positive breast cancer cells

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL S100A7 is a member of the S100 protein family which is characterized by two calcium-binding sites of the helix-loop-helix (EF-hand type) conformation. It is a part of the S100 gene cluster located on human chromosome 1q21, which constitutes the epidermal differentiation complex. This region is of particular interest as it encodes many genes that have been linked to epidermal differentiation. S100A7 is also associated with several epithelial malignancies including breast cancer. It is highly expressed in ductal carcinoma in situ and a subset of invasive breast cancers. S100A7 is mainly associated with the worst prognosis in invasive estrogen receptor α negative (ERα−) breast cancers, however, its exact role in ERα+ breast cancers is not known. Therefore, in the present study, we investigated the tumorigenic potential of S100A7 overexpression in ERα+ breast cancer cells. The tumorigenicity of stably overexpressing S100A7 and vector control ERα+ cell lines was assessed using proliferation, migration and wound healing assays. The results showed that S100A7 overexpression decreased epidermal growth factor (EGF)-mediated proliferation in MCF7 and T47D cells. Further, in these cells, EGF-induced migration and wound healing ability were inhibited in S100A7 overexpressing cells compared to the vector control. Characterization of the EGF-mediated signaling pathways revealed reduced phosphorylation/activation of various signaling molecules in S100A7 overexpressing cells. Morphological examination of the cells revealed decreased lamellipodia formation in S100A7 overexpressing MCF7 cells compared to vector control. This led us to hypothesize that S100A7 may be regulating the actin polymerization and cytoskeletal dynamics in ERα+ cells. Actin staining (Phalloidin) showed increased actin polymerization on the lamellipodia and membrane in vector control MCF7 compared to S100A7 overexpressing cells. Further elucidation of signalling revealed that S100A7 overexpression decreased EGF-induced GTPase Rac activation. Rac is an important regulator of actin dynamics. We also observed that S100A7 overexpression reduced the activation of Lim-Kinase as well as cofilin which are downstream targets of Rac activation. Taken together, these results show that S100A7 overexpression may modulate cytoskeletal dynamics by regulating Rac activation in ERα+ cells. The reduced actin polymerization may be responsible for the decreased lamellipodia formation as well as the reduced migration and would healing ability of ERα+ cells. S100A7 has been shown to enhance EGF-induced signaling and functional effects in ERα− cells. However, we observed that S100A7 decreases EGF-induced signaling and functional effects in ERα+ cells. This suggests that S100A7 may have a differential role in modulating EGF-induced signaling in ERα+ cells compared to ERα− cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 480. doi:1538-7445.AM2012-480