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Ral proteins are found in GTP\u2010bound active and GDP\u2010bound inactive forms. The activation process is executed by guanine nucleotide exchange factors, while inactivation is mediated by GTPase\u2010activating proteins (GAPs). RalGAPs are complexes that consist of a catalytic \u03b11 or \u03b12 subunit together with a common \u03b2 subunit. Several reports implicate the importance of Ral in pancreatic ductal adenocarcinoma (PDAC). However, there are few reports on the relationship between levels of RalGAP expression and malignancy in PDAC. We generated RalGAP\u03b2\u2010deficient PDAC cells by CRISPR\u2010Cas9 genome editing to investigate how increased Ral activity affects malignant phenotypes of PDAC cells. RalGAP\u03b2\u2010deficient PDAC cells exhibited several\u2010fold higher Ral activity relative to control cells. They had a high migratory and invasive capacity. The RalGAP\u03b2\u2010deficient cells grew more rapidly than control cells when injected subcutaneously into nude mice. When injected into the spleen, the RalGAP\u03b2\u2010deficient cells formed larger splenic tumors with more liver metastases, and unlike controls, they disseminated into the abdominal cavity. These results indicate that RalGAP\u03b2 deficiency in PDAC cells contributes to high activities of RalA and RalB, leading to enhanced cell migration and invasion in vitro, and tumor growth and metastasis in vivo.<\/jats:p>","DOI":"10.1111\/cas.14970","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T15:45:53Z","timestamp":1621439153000},"page":"3064-3073","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Ral GTPase\u2013activating protein regulates the malignancy of pancreatic ductal adenocarcinoma"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8823-6696","authenticated-orcid":false,"given":"Shingo","family":"Yoshimachi","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biology Institute of Development, Aging and Cancer Tohoku University Sendai Japan"},{"name":"Department of Surgery Tohoku University Graduate 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