Multi-omics Profiling Shows BAP1 Loss Is Associated with Upregulated Cell Adhesion Molecules in Uveal Melanoma

Usman Baqai, Timothy J. Purwin, Nelisa Bechtel, Vivian Chua, Anna Han, Edward J. Hartsough, Jeffim N. Kuznetsoff, J. William Harbour, Andrew E. Aplin

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that is mutated in cancer, including uveal melanoma. Loss-of-function BAP1 mutations are associated with uveal melanoma 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 uveal melanoma patient samples is associated with upregulated gene expression of multiple cell adhesion molecules (CAM), including E-cadherin (CDH1), cell adhesion molecule 1 (CADM1), and syndecan-2 (SDC2). Similar findings were observed in uveal melanoma cell lines and single-cell RNA-sequencing data from uveal melanoma patient samples. BAP1 reexpression in uveal melanoma 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 uveal melanoma cells. Together, our findings demonstrate that BAP1 regulates the expression of CAMs which may regulate metastatic traits. IMPLICATIONS: BAP1 mutations and increased metastasis may be due to upregulation of CAMs.

Original languageEnglish (US)
Pages (from-to)1260-1271
Number of pages12
JournalMolecular cancer research : MCR
Volume20
Issue number8
DOIs
StatePublished - Aug 5 2022
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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