Panelo Laura C, Machado Mileni Soares, Rubio María F, Jaworski Felipe, Alvarado Cecilia V, Paz Leonardo A, Urtreger Alejandro J, Vazquez Elba, Costas Mónica A
Laboratorio de Biología Moleculary Apoptosis, Instituto de Investigaciones Médicas Alfredo Lanari, IDIM-CONICET, Facultad de Medicina, Universidad de Buenos Aires, C1427ARO Buenos Aires, Argentina.
Laboratorio de Inflamación y Cancer, IQUIBICEN-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
Oncotarget. 2017 Dec 22;9(5):5848-5860. doi: 10.18632/oncotarget.23635. eCollection 2018 Jan 19.
RAC3 is a transcription coactivator, usually overexpressed in several tumors and required to maintain the pluripotency in normal stem cells. In this work we studied the association between RAC3 overexpression on cancer cell stemness and the capacity of this protein to induce cancer stem properties in non tumoral cells. We performed and experiments using two strategies: by overexpressing RAC3 in the non tumoral cell line HEK293 and by silencing RAC3 in the human colorectal epithelial cell line HCT116 by transfection. Furthermore, we analysed public repository microarrays data from human colorectal tumors in different developmental stages. We found that RAC3 overexpression was mainly associated to CD133+ side-population of colon cancer cells and also to early and advanced stages of colon cancer, involving increased expression of mesenchymal and stem markers. In turn, RAC3 silencing induced diminished tumoral properties and cancer stem cells as determined by Hoechst efflux, tumorspheres and clonogenic growth, which correlated with decreased Nanog and OCT4 expression. In non tumoral cells, RAC3 overexpression induced tumoral transformation; mesenchymal phenotype and stem markers expression. Moreover, these transformed cells generated tumors . Our results demonstrate that RAC3 is required for maintaining and induction of cancer cell stemness.
RAC3是一种转录共激活因子，通常在多种肿瘤中过表达，并且是维持正常干细胞多能性所必需的。在这项研究中，我们研究了RAC3过表达与癌细胞干性之间的关联，以及该蛋白在非肿瘤细胞中诱导癌症干细胞特性的能力。我们采用两种策略进行了实验：通过在非肿瘤细胞系HEK293中过表达RAC3，以及通过转染在人结肠上皮细胞系HCT116中沉默RAC3。此外，我们分析了来自不同发育阶段人类结肠肿瘤的公共存储库微阵列数据。我们发现，RAC3过表达主要与结肠癌细胞的CD133 + 侧群相关，也与结肠癌的早期和晚期相关，涉及间充质和干细胞标志物表达增加。反过来，RAC3沉默导致肿瘤特性和癌症干细胞减少（通过Hoechst外排、肿瘤球和克隆生长测定），这与Nanog和OCT4表达降低相关。在非肿瘤细胞中，RAC3过表达诱导肿瘤转化、间充质表型和干细胞标志物表达。此外，这些转化细胞形成了肿瘤。我们的结果表明，RAC3是维持和诱导癌细胞干性所必需的。
