A sugar molecule, hyaluronan (HA) promotes growth, invasion, therapy resistance and stemness in ovarian cancer cells. The Notch3 signalling pathway also promotes and maintains cancer stem cell populations and is associated with poor prognosis in ovarian cancer patients. For this study, we determined the effects of different molecular weight HA on ovarian cancer cells overexpressing the intracellular domain (NICD3) of notch 3. 1000kDa HA significantly enhanced spheroid formation of ES-2NICD3 overexpression cells combined with parental ES-2 cells at a ratio of 3:1. We analysed protein expression in these spheroids using mass spectrometry and identified a protein of interest, disabled homolog 2 (DAB2) was enhanced by 1000kDa HA. DAB2 is typically recognised as a tumour suppressor in ovarian cancer, however, some studies have demonstrated pro-metastatic effects. We found that DAB2 expression is associated with poor outcome in patients with high grade serous ovarian cancer (HGSOC). DAB2 stromal expression was also significantly increased in ovarian cancer patient tissues at relapse compared to diagnosis. DAB2 was decreased in tumour compared to normal tissues, interestingly DAB2 was increased in metastatic tumours compared to primary tumours (GENT2 and GSE2109 databases). DAB2 expression was positively correlated with epithelial to mesenchymal transition markers in ovarian cancer cell lines (cBioportal, TGCA, n=59) and HGSOC patient tissues (cBioportal, TGCA, n=174-551). Overexpression of DAB2 in A2780 cells significantly reduced cell proliferation, increased sensitivity to carboplatin and reduced cell invasion in vivo. In OVCAR3 cells, DAB2 overexpression didn’t affect cell proliferation but reduced sensitivity to carboplatin and cell motility and invasion in vitro and in vivo. Functional experiments support a tumor suppressive role of DAB2 in ovarian cancer. Interestingly, patient and cell line expression data suggest a relationship between DAB2 and ovarian cancer progression. We hypothesise a pro-tumorigenic role of DAB2 in the tumor microenvironment in ovarian cancer.