RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.

doi:10.1126/sciadv.adz6907

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Article

RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.

Science advances - 25 Sept 2026

De Silva Pushpamali, Fitzgerald Samantha, Cazaubiel Jules, Qian Kristin, Hofree Matan, Lin Jia-Ren, Pelletier Roxanne, Lopez Leon Mariana, Ho Phuong Vu Mai, Takashima Yasutoshi, Väyrynen Juha P, Matsuda Kosuke, Ugai Tomotaka, Ford-Roshon Dane, Bala Pratyusha, Hacohen Nir, Ng Kimmie, Nowak Jonathan A, Ogino Shuji, Sorger Peter K, Giannakis Marios

Abstract excerpt

The RNF43 p.G659fs (RNF43659mut) mutation occurs in 8% of colorectal cancers (CRCs) and is enriched in microsatellite instability-high (MSI-H) tumors. Although RNF43659mut promotes tumor growth through phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) activation independent of WNT signaling, its immunologic effects are poorly defined. We show that RNF43659mut shapes an...

Read the complete abstract on PubMed

Topics

Humans
Killer Cells, Natural
TOR Serine-Threonine Kinases
Colorectal Neoplasms

Methodology Data sources Editorial policy Privacy Delete account & data About Contact Helena Bioinformatics

Proto-Oncogene Proteins c-akt

Signal Transduction

Phosphatidylinositol 3-Kinases

Microsatellite Instability

HLA-E Antigens

Histocompatibility Antigens Class I

Up-Regulation

Ubiquitin-Protein Ligases

Cell Line, Tumor

Gene Expression Regulation, Neoplastic

Mutation

DNA-Binding Proteins

Source

Open in PubMed Open full text

Identifiers

PMID: 42777043
DOI: 10.1126/sciadv.adz6907
PMCID: PMC13600164

Genes

RNF43

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 21 Oct 2026.

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