Journal article
Multi-omics profiling shows BAP1 loss is associated with upregulated cell adhesion molecules in uveal melanoma
Molecular cancer research, v 20(8), pp OF1-OF12
15 Apr 2022
PMID: 35426938
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 upregulated gene expression 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 scRNA seq data from UM 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. Implications: BAP1 mutations and increased metastasis may be due to upregulation of cell adhesion molecules.
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Details
- Title
- Multi-omics profiling shows BAP1 loss is associated with upregulated cell adhesion molecules in uveal melanoma
- Creators
- Usman Baqai - Thomas Jefferson UniversityTimothy J Purwin - Thomas Jefferson UniversityNelisa Bechtel - Thomas Jefferson UniversityVivian Chua - Thomas Jefferson UniversityAnna Han - Thomas Jefferson UniversityEdward J Hartsough - Drexel UniversityJeffim N Kuznetsoff - University of Miami, Miami, FL, United StatesJ William Harbour - Southwestern Medical CenterAndrew E Aplin - Thomas Jefferson University
- Publication Details
- Molecular cancer research, v 20(8), pp OF1-OF12
- Publisher
- American Association for Cancer Research (AACR)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000837267600001
- Scopus ID
- 2-s2.0-85135575668
- Other Identifier
- 991019168314804721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology
- Oncology