RNF43

Last update 08 May 2025

Basic Info

Synonyms

DKFZp781H0392, E3 ubiquitin-protein ligase RNF43, FLJ20315

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Introduction

E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination, endocytosis and subsequent degradation of Wnt receptor complex components Frizzled. Acts on both canonical and non-canonical Wnt signaling pathway (PubMed:18313049, PubMed:22575959, PubMed:22895187). Along with RSPO2 and ZNRF3, constitutes a master switch that governs limb specification (By similarity).

100 Clinical Results associated with RNF43

100 Translational Medicine associated with RNF43

0 Patents (Medical) associated with RNF43

425

Literatures (Medical) associated with RNF43

15 Apr 2025·International Journal of Cancer

Comprehensive characterization of MCL‐1 in patients with colorectal cancer: Expression, molecular profiles, and outcomes

Article

Author: Weinberg, Benjamin A. ; Zhang, Wu ; Lo, Jae Ho ; Zhang, Lin ; Shields, Anthony F. ; Soni, Shivani ; Jayachandran, Priya ; Xiu, Joanne ; Lenz, Heinz‐Josef ; Ashouri, Karam ; Baca, Yasmine ; Goldberg, Richard M. ; Farrell, Alex ; Algaze, Sandra ; Battaglin, Francesca ; Goel, Sanjay ; Wong, Alexandra ; Yu, Jian ; Lou, Emil ; Singh, Indrakant K. ; Torres‐Gonzalez, Lesly ; Marshall, John L. ; Mittal, Pooja

AbstractMyeloid cell leukemia 1 (MCL‐1) is a member of the B‐cell lymphoma 2 protein family and has anti‐apoptotic functions. Deregulation of MCL‐1 has been reported in several cancers, including lung and breast cancer. In the present study, the association of MCL‐1 expression with molecular features in colorectal cancer (CRC) has been highlighted. CRC samples from Caris Life Sciences (Phoenix, AZ) were analyzed using NextGen DNA sequencing, whole transcriptome sequencing, whole exome sequencing, and immunohistochemistry (IHC); and stratified based on MCL‐1 expression as top quartile MCL‐1high (Q4) and bottom quartile MCL‐1low (Q1). Immune cell infiltration (CI) in the tumor microenvironment (TME) was measured using RNA deconvolution analysis (QuanTIseq). MCL‐1high tumors were associated with an increased rate of programmed death ligand 1 IHC, higher T cell‐inflamed signature, interferon score, microsatellite instability‐high and tumor mutational burden‐high status. MCL‐1high was associated with higher mutation rates of BCOR, TP53, KMT2D, ASXL1, KDM6A, ATM, MSH6, SPEN, KRAS, STK11, GNAS, RNF43, and lower mutation rates of CDKN1B, NRAS, and APC, and copy number amplifications in several genes. MCL‐1high TME had higher CI of M1 and M2 macrophages, B cells, natural killer cells, neutrophils, and T‐regulatory cells infiltration, and lower CI of myeloid dendritic cells. Higher MCL‐1 expression is significantly associated with favorable clinical outcomes in CRC cohorts. Our data showed a strong correlation between MCL‐1 and distinct immune biomarkers and TME CI in CRC. Our findings suggest MCL‐1 is a potential modulator of antitumor immunity, TME, and biomarker in CRC.

07 Apr 2025·Oncogene

Lack of dominant-negative activity for tumor-related ZNRF3 missense mutations at endogenous levels

Article

Author: van Merode, Jenna ; de Schipper, Nicky ; Smits, Ron ; van de Kamp, Lisa ; Neves Cabrita, Madalena ; Peppelenbosch, Maikel P ; Zhang, Ruyi ; Massaar, Sanne ; Niu, Jiahui ; Li, Shanshan

AbstractZNRF3, a negative regulator of β-catenin signaling, removes Wnt receptors from the membrane. Currently, it is unknown which tumor-associated variants can be considered driver mutations and through which mechanisms they contribute to cancer. Here we show that all truncating mutations analyzed at endogenous levels exhibit loss-of-function, with longer variants retaining partial activity. Regarding missense mutations, we show that 27/82 ZNRF3 variants in the RING and R-Spondin domain structures, lead to (partial) loss-of-function/hyperactivation. Mechanistically, defective R-Spondin domain variants appear to undergo endoplasmic-reticulum-associated degradation due to protein misfolding, leading to reduced protein levels. They fail to reach the membrane correctly, which can be partially restored for several variants by culturing cells at 27 °C. Although RING and R-Spondin domain mutations in RNF43/ZNRF3 are often considered to possess dominant-negative oncogene-like activity in cancers, our findings challenge this notion. When representative variants are heterozygously introduced into endogenous ZNRF3, their impact on β-catenin signaling mirrors that of heterozygous knockout, suggesting that the supposed dominant-negative effect is non-existent. In other words, so-called “hyperactivating” ZNRF3/RNF43 mutations behave as classical loss-of-function mutations at endogenous levels.

01 Apr 2025·Cancer Science

Identification of clinicopathological‐specific driver gene and genetic subtyping of colorectal cancer

Article

Author: Li, Jianjiong ; Yin, Jiani C. ; Huang, Xianqiang ; Gan, Meifu ; Wang, Chunnian ; Pang, Jiaohui ; Li, Ningyou ; Hong, Xinyue ; Yuan, Danping ; Bao, Hua ; Yang, Changshun ; Gong, Wei

AbstractThis study analyzed targeted sequencing data from 6530 tissue samples from patients with metastatic Chinese colorectal cancer (CRC) to identify low mutation frequency and subgroup‐specific driver genes, using three algorithms for overall CRC as well as across different clinicopathological subgroups. We analyzed 425 cancer‐related genes, identifying 101 potential driver genes, including 36 novel to CRC. Notably, some genes demonstrated subgroup specificity; for instance, ERBB4 was found as a male‐specific driver gene and mutations of ERBB4 only influenced the prognosis of male patients with CRC. This sex disparity of ERBB4 was validated in an independent large‐scale Memorial Sloan Kettering Cancer Center CRC cohort with 2444 samples. Furthermore, using network‐based stratification based on protein–protein interaction, we classified the microsatellite stable (MSS) and unstable (MSI) CRCs into six and three major subtypes, respectively, each showing unique phenotypes and prognoses. In MSS CRC, cluster 5 (APCAMER1–KRAS) and cluster 2 (RNF43–BRAF–PIK3CA) were predominant, and cluster 5 showed a superior overall survival compared with cluster 2. This extensive heterogeneity in driver gene mutations underscores the complexity of CRC and suggests significant implications for treatment and prognostic assessments.

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RNF43

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