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ILC is distinguished by discohesive, single-file growth from loss of E-cadherin (CDH1). Few ILC cell lines exist, limiting mechanistic study of this understudied disease. Here we describe WCRC-25, a novel ILC cell line established from a pleural effusion of a patient with metastatic ILC. While WCRC-25 lacks ER expression, it is molecularly defined as luminal with Her2-like features, and shows anchorage-independent growth and haptotactic migration toward Collagen I. Sequencing identified a CDH1 Q706* truncating mutation alongside FOXA1, CTCF, BRCA2 and TP53 mutations shared with the patient's metastases, while copy-number and optical genome mapping revealed structural rearrangements typical of ILC. Transcriptomic AKT-pathway signatures predicted, and cell-based assays confirmed, sensitivity to PI3K\/AKT inhibition. WCRC-25 also engrafted and spontaneously metastasized in vivo. WCRC-25 is a valuable new tool for dissecting ILC biology and therapeutic vulnerabilities.<\/jats:p>","DOI":"10.1101\/2023.09.15.558023","type":"posted-content","created":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T17:45:10Z","timestamp":1694972710000},"source":"Crossref","is-referenced-by-count":2,"title":["WCRC-25: A novel luminal Invasive Lobular Carcinoma cell line model"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5113-0970","authenticated-orcid":false,"given":"Ashuvinee","family":"Elangovan","sequence":"first","affiliation":[{"name":"University of Pittsburgh;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily A","family":"Bossart","sequence":"additional","affiliation":[{"name":"University of 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