Similar to RUNX1, the strongest 
evidence for a pro-oncogenic function for RUNX2 comes from studies in lymphoma/leukemia models; however RUNX2 was also shown to play a role in invasive bone, breast, prostate, thyroid and pancreatic cancer. Lately, RUNX2 expression was also associated with EOC tumor progression and poor prognosis. This prompted us to investigate if RUNX2 is induced due to hypomethylation in advanced EOC and whether the RUNX2 gene is functionally implicated in EOC tumorigenesis, including disease progression and response to treatment. Here we show that, similar to RUNX1, the RUNX2 gene is functionally involved in EOC cell proliferation, migration and invasion. However, we also demonstrate that RUNX1 and RUNX2 employ molecular mechanisms in EOC dissemination that are specific for each gene. Snap frozen and formalin-fixed paraffin-embedded tissues of 117 serous EOC tumors were provided by the Banque de tissus et de donne��es of the Re��seau de recherche sur le cancer of the Fonds de recherche du Que��bec – Sante�� at the Hotel-Dieu de Quebec Hospital, Quebec, Canada, which is affiliated with the Canadian Tumor Repository Network. These clinical specimens included 13 borderline, or low-malignant potential tumors, 52 high-grade adenocarcinomas and 52 omental metastases. None of the patients received chemotherapy before surgery. All tumors were histologically classified according to the criteria defined by the World Health Organization. The CT treatment was completed for all patients and the response to treatment was known. Disease progression was evaluated following the guidelines of the Gynecology Cancer Intergroup. Progression free survival was defined as the time from surgery to the first observation of disease progression, recurrence or death. Thirteen normal ovarian samples and 13 normal uterine smooth muscle samples were derived from women subjected to hysterectomy with oophorectomy due to non-ovarian pathologies. TMAs were constructed, as previously described. Briefly, one representative block of each ovarian tumor and normal ovarian tissue was selected for the preparation of the tissue arrays. Three 0.6 mm cores of tumor were taken from each tumor block and placed, 0.4 mm apart, on a recipient paraffin block using a commercial tissue arrayer. The cores were randomly placed on one of two recipient blocks to avoid IHC evaluation biases. Four micron thick sections were cut for the hematoxylin-eosin staining and IHC analyses. IHC was performed, as previously described. Briefly, 4 mm tissue sections were deparaffinized and then heated in an autoclave for 12 min to retrieve the antigenicity before blocking with endogenous peroxidase. We investigated the impact of RUNX2 gene suppression on SKOV3 cell proliferation, cell cycle control, migration, invasion and sensitivity to cisplatin and paclitaxel. The RUNX2 gene knockdown led to a sharp decrease of the number of viable adherent cells, compared to control cells. This observation was further supported by the colony formation assay showing that the numbers of Albaspidin-AA clones formed by cells with stably reduced RUNX2 expression were significantly lower than that of control cells. Taken together, our observations strongly indicate an influence of RUNX2 transcripts on EOC cell proliferation and further on their Tulathromycin B propensity to form colonies. Moreover, RUNX2 suppression significantly inhibited both migration and invasion of SKOV3 cells. As shown in Figure 5A and 5B, the numbers of SKOV3 cells that passed through the filter using shRNA clones 3 and 6 were remarkably less than that in the control clone, which is indicative for a role for RUNX2 in the regulation of invasion and migration in EOC. Similar results were obtained upon RUNX2 knockdown in A2780s cells. Finally, RUNX2 suppression had no significant impact on SKOV3 cell cycle control and cisplatin and paclitaxel sensitivity.