Multi-omics profiling shows BAP1 loss is associated with upregulated cell adhesion molecules in uveal melanoma.

BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that is mutated in cancer, including uveal melanoma (UM). Loss-of-function BAP1 mutations are associated with UM metastasis and poor prognosis, but the mechanisms underlying these effects remain unclear. Upregulation of cell-cell adhesion proteins is involved with collective migration and metastatic seeding of cancer cells. Here, we show that BAP1 loss in UM patient samples is associated with an upregulated gene expression profile of multiple cell adhesion molecules (CAMs), including E-cadherin (CDH1), cell adhesion molecule 1 (CADM1), and syndecan-2 (SDC2). Similar findings were observed in UM cell lines and single cell RNA sequencing data from patient samples. BAP1 re-expression in UM cells reduced E-cadherin and CADM1 levels. Functionally, knockdown of E-cadherin decreased spheroid cluster formation and knockdown of CADM1 decreased growth of BAP1 mutant UM cells. Together, our findings demonstrate that BAP1 regulates the expression of CAMs which may regulate metastatic traits.