Abstract B54: Squamous cell carcinoma antigen 1 (SCCA1) promotes mammary tumorigenesis through the induction of misfolded protein stress

摘要: SCCA1, a member of the serine/cysteine protease inhibitor family, is upregulated in several cancers such as cervix, lung, head and neck, liver, skin, breast, has been used diagnostic/prognostic marker. However, biological function SCCA1 tumorigenesis remains largely unclear. Here we show that ectopic expression non-tumorigenic mammary epithelial cell line MCF10A leads to spindle shaped morphology, increased migration, resistance anoikis, foci formation soft agar, well orthotopic tumor immune-compromised mice. Gene analysis revealed induces changes are associated with epithelial-mesenchymal transition (EMT). Mechanistically, interferes cellular protein homeostasis leading heightened unfolded response including nuclear translocation transcriptionally active form ATF6α. This ATF6α signaling results NF-κB activation pro-inflammatory an IL-6 autocrine loop drives EMT transformation. These findings indicate previously unknown role promoting by inducing misfolded stress, activation, pro-tumorigenic cytokine signaling. Citation Format: Namratha Sheshadri, Erica Ullman, Joseph Catanzaro, Ji-An Pan, Emily Chen, Wei-Xing Zong. Squamous carcinoma antigen 1 (SCCA1) promotes through induction stress. [abstract]. In: Proceedings Third AACR International Conference on Frontiers Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Res 2013;73(19 Suppl):Abstract nr B54.