The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSCs that is also capable of differentiating into non-self -renewing cell populations that constitute the bulk tumor mass. These cells have stem cell characteristics and may play a role in tumorigenic growth, metastasis, and therapeutic resistance. Here we interrogated the oncogenic roles of PSMD2, a subunit of the 19S regulatory complex of proteasomes, as a constituent of a signature is a candidate oncogene in breast cancer. PSMD2 is required for breast CSCs proliferation both in vitro and in vivo, as shRNA-mediated PSMD2 silencing attenuated tumor growth. Further, PMSD2 is sufficient to induce stem cell characteristics, as forced PSMD2 expression facilitated mammosphere formation and increased the CD44+ breast CSC-like population. Mechanistically, the action of PSMD2 for induction of breast stemness is mediated by transcriptional regulation of the Notch signaling pathway and PSMD2 inhibition were associated with changes in epithelial-mesenchymal transition (EMT) phenotype. Knockdown of PSMD2 induced dramatic morphological changes, the typical spindle-like appearance cells was replaced with the round shape, like epithelial morphology. Moreover, treatment of TGF-β, the main inducer of EMT, lead to increased expression of PSMD2. PSMD2 silencing up-regulated E-cadherin and down-regulated expression of vimentin, N-cadherin and snail, mesenchymal markers. Clinically, PSMD2 expression was elevated in basal-like TNBC (triple negative breast cancer), correlated with poor prognosis, insilico analysis on a dataset comprising over 2413 microarrays of the web application bc-GenExMiner. Altogether, our findings suggest that PSMD2 may be a good molecular target candidate and PSMD2 inhibitor may kills breast CSCs and ameliorates poor prognosis of breast cancer.

Note: This abstract was not presented at the conference.

Citation Format: Kyung-Min Lee, So-Youn Jung, Seolwha Jo, Eunji Kang, Dong-Young Noh, Wonshik Han. PSMD2 is a molecular marker for a poor prognosis and determines cancer stem cells traits in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr B22.