Abstract Tumor metastasis, the spread of tumor cells to distant tissues from its site of initiation is a multi-step and multi-factorial process. Hyperactivation of RAS pathway is reported in >50% of different cancers and is associated with metastasis and poor prognosis. Since Ras signaling pathway is essential for normal development, its been difficult to develop drugs against it in tumors. This led to the identification of several Ras effectors. Ras association (RalGDS/AF-6) domain family (RASSF) proteins are non-enzymatic effectors of Ras. RASSF7 is a member of the less characterized N-terminal RASSFs. Similar to other RASSFs, RASSF7 also associates with Ras. Several mutations within RASSF7 open reading frame as well as differential expression pattern were observed in various tumors. The role of RASSF7 and its downstream signaling is not yet clearly understood. Microarray analysis for RASSF7 identified several differentially regulated genes with enrichment for pathways including cell adhesion, inflammation, actin cytoskeleton and cell-cell communication suggesting that RASSF7 might regulate cell migration. Ectopic expression of RASSF7 inhibited cell migration of multiple cancer cell lines in vitro. RT-qPCR and western blotting analysis suggest that RASSF7 can transcriptionally upregulate Notch1 expression. Knockdown of Notch1 abrogated RASSF7 mediated inhibition of cell migration. Our experiments suggest that RASSF7 alters the localization of Notch1. Cross-talk Notch signaling is a key signaling pathway regulating tumor progression across several different cancers. Collectively, our data suggests that RASSF7 impinges on Notch1 to regulate cell migration. Citation Format: Lakshmi R. Perumalsamy, Mahalingam S. Ras association (RalGDS/AF-6) domain family member integrates with notch signaling to regulate tumor cell migration. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5076.