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

Poster Board Number: A210

Usman Baqai (Thomas Jefferson University), Timothy Purwin (Thomas Jefferson University), Vivian Chua (Thomas Jefferson University), Anna Han (Jeonbuk National University, Jeonbuk National University), Nelisa Bechtel (Thomas Jefferson University), Edward Hartsough (Drexel University College of Medicine), Jeffim Kuznetsoff (Bascom Palmer Eye Institute University of Miami Miller School of Medicine), J. Harbor (UT Southwestern Medical Center), Andrew Aplin (Thomas Jefferson University)

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.

Support or Funding Information

This work was supported by National Institutes of Health (NIH)/National Cancer Institute (NCI) grants R01s, CA253977 and CA257505, and P01 CA114046 project 4 to A.E.A. In addition, the work was supported by NIH/NCI R00 CA207855 and the W.W. Smith Charitable Trusts grants to E.J.H. This work was also supported by the Melanoma Research Foundation Medical Student Award 2020 to U.B. The Sidney Kimmel Cancer Center Flow Cytometry and Translational Pathology core facilities are supported by NIH/NCI (P30 CA056036). The RPPA studies were performed at the Functional Proteomics Core Facility at The University of Texas, MD Anderson Cancer Center, which is supported by an NCI Cancer Center Support Grant (P30 CA16672).