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Updated: Sep 4, 2025
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Melanoma RBPome identification reveals PDIA6 as an unconventional RNA-binding protein involved in metastasis
Neus Mestre-Farràs1, Santiago Guerrero1, Nadine Bley2
1Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain.
Abstract:
RNA-binding proteins (RBPs) have been relatively overlooked in cancer research despite their contribution to virtually every cancer hallmark. Here, we use RNA interactome capture (RIC) to characterize the melanoma RBPome and uncover novel RBPs involved in melanoma progression. Comparison of RIC profiles of a non-tumoral versus a metastatic cell line revealed prevalent changes in RNA-binding capacities that were not associated with changes in RBP levels. Extensive functional validation of a selected group of 24 RBPs using five different in vitro assays unveiled unanticipated roles of RBPs in melanoma malignancy. As proof-of-principle we focused on PDIA6, an ER-lumen chaperone that displayed a novel RNA-binding activity. We show that PDIA6 is involved in metastatic progression, map its RNA-binding domain, and find that RNA binding is required for PDIA6 tumorigenic properties. These results exemplify how RIC technologies can be harnessed to uncover novel vulnerabilities of cancer cells.
Insights
Researchers identified novel RNA-binding proteins (RBPs) critical for melanoma progression using RNA interactome capture. These RBPs, including PDIA6, offer new therapeutic targets by revealing vulnerabilities in cancer cells.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- RNA-binding proteins (RBPs) play crucial roles in cancer but are understudied.
- Understanding the RBPome in melanoma is essential for identifying novel therapeutic targets.
Purpose of the Study:
- To characterize the melanoma RBPome using RNA interactome capture (RIC).
- To identify novel RBPs involved in melanoma progression and malignancy.
- To functionally validate identified RBPs, focusing on PDIA6.
Main Methods:
- RNA interactome capture (RIC) to profile RBPs in melanoma cell lines.
- Comparison of RBP profiles between non-tumoral and metastatic melanoma cells.
- In vitro assays for functional validation of 24 selected RBPs.
- Detailed investigation of PDIA6, including RNA-binding domain mapping.
Main Results:
- RIC revealed significant changes in RNA-binding capacities of RBPs during melanoma progression, independent of RBP levels.
- Functional validation identified unexpected roles for several RBPs in melanoma malignancy.
- PDIA6, an ER-lumen chaperone, was identified as a novel RNA-binding protein crucial for melanoma metastasis.
- RNA binding by PDIA6 was essential for its tumorigenic properties.
Conclusions:
- RIC is a powerful technology for uncovering the melanoma RBPome and identifying novel cancer vulnerabilities.
- Targeting specific RBPs, such as PDIA6, may represent a promising therapeutic strategy for melanoma.
