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Cell communication mediated by growth factors and steroid hormones plays a critical role in regulating proliferation, migration and survival. Dysregulation of these signaling pathways is commonly implicated in the progression of cancer. Among steroid hormones, vitamin D metabolites, in particular 1α,25-dihydroxyvitamin D₃ have demonstrated anti-tumor properties. In paper I, we investigated the effects of 1α,25-dihydroxyvitamin D₃ and its analog tacalcitol on cell signaling and anchorage-independent growth in glioblastoma cell lines T98G and U251. Both compounds modulated key signaling proteins, including STAT3 and suppressed anchorage-independent growth, supporting their potential to reduce tumorigenicity in glioblastoma. The effects of tacalcitol were stronger than for 1α,25-dihydroxyvitamin D₃, indicating that even minor modifications of vitamin D can impact its effect on signaling. In paper II, we explored the role of protein disulphide-isomerase A3 (PDIA3), an alternative receptor for 1α,25-dihydroxyvitamin D₃-mediated signaling. Silencing PDIA3 in prostate cancer (PC3, DU145) cells disrupted proliferation, increased migration, and altered the expression of vitamin D-regulating enzymes and transcription factors. Cellular thermal shift assay indicated that 1α,25-dihydroxyvitamin D₃ directly or indirectly interacts with PDIA3, suggesting PDIA3 involvement in mediating 1α,25-dihydroxyvitamin D₃ responses. In paper III, we studied the crosstalk between 1α,25-dihydroxyvitamin D₃ and the growth factors epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) -BB in U2OS cells. EGF enhanced vitamin D-induced expression of the catabolic enzyme CYP24A1 via AKT and ERK1/2 pathways, while 1α,25-dihydroxyvitamin D₃ suppressed PDGF-induced proliferation and receptor phosphorylation, highlighting reciprocal regulation between 1α,25-dihydroxyvitamin D₃ and growth factor signaling. In paper IV, we examined the effects of the oxidized cholesterol derivative 24-hydroxycholesterol in T98G glioblastoma cells. 24-hydroxycholesterol altered the cell morphology, suppressed proliferation and enhanced migration. 24-hydroxycholesterol increased the expression of epithelial-to-mesenchymal transition markers in a liver X receptor (LXR)-dependent manner. This thesis provides insight into the effects of 1α,25-dihydroxyvitamin D₃-mediated signaling in the regulation of cancer cell behavior and crosstalk with growth factor signaling involving EGF and PDGF. The thesis supports the role of PDIA3 in 1α,25-dihydroxyvitamin D₃-signaling responses. By modulating key pathways that control proliferation, migration, and differentiation, 1α,25-dihydroxyvitamin D₃ and vitamin D analogs demonstrate mechanisms that may contribute to anti-cancer activity and offer potential targets for therapeutic intervention.