<scp>FAM</scp>83 family oncogenes are broadly involved in human cancers: an integrative multi‐omics approach

Snijders, Antoine M.; Lee, Sun-Young; Hang, Bo; Hao, Wenshan; Bissell, Mina J.; Mao, Jian‐Hua

doi:10.1002/1878-0261.12016

Cited by 98 publications

(113 citation statements)

References 32 publications

(57 reference statements)

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“…The FAM83 proteins were recently identified as novel transforming oncogenes that function as intermediaries in EGFR/RAS signaling, and the oncogenic properties were dependent upon the conserved DUF1669 domain (Cipriano et al, , ). It was also demonstrated that these proteins, including FAM83H, were overexpressed in many human tumors (Cipriano et al, ; Snijders et al, ). Therefore, FAM83H might play a role in cell proliferation or survival mediated by EGFR/RAS signaling, presumably through its DUF1669 domain, which is essential for certain critical physiological functions.…”

Section: Discussionmentioning

confidence: 98%

The Enamel Phenotype in Homozygous Fam83h Truncation Mice

Wang

Smith

et al. 2019

Molec Gen & Gen Med

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Background Truncation FAM83H mutations cause human autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI), an inherited disorder characterized by severe hardness defects in dental enamel. No enamel defects were observed in Fam83h null mice suggesting that Fam83h truncation mice would better replicate human mutations. Methods We generated and characterized a mouse model (Fam83hTr/Tr) expressing a truncated FAM83H protein (amino acids 1–296), which recapitulated the ADHCAI‐causing human FAM83H p.Tyr297* mutation. Results Day 14 and 7‐week Fam83hTr/Tr molars exhibited rough enamel surfaces and slender cusps resulting from hypoplastic enamel defects. The lateral third of the Fam83hTr/Tr incisor enamel layer was thinner, with surface roughness and altered enamel rod orientation, suggesting disturbed enamel matrix secretion. Regular electron density in mandibular incisor enamel indicated normal enamel maturation. Only mildly increased posteruption attrition of Fam83hTr/Tr molar enamel was observed at 7‐weeks. Histologically, the Fam83hTr/Tr enamel organ, including ameloblasts, and enamel matrices at sequential stages of amelogenesis exhibited comparable morphology without overt abnormalities, except irregular and less evident ameloblast Tomes' processes in specific areas. Conclusions Considering Fam83h−/− mice showed no enamel phenotype, while Fam83hTr/Tr (p.Tyr297*) mice displayed obvious enamel malformations, we conclude that FAM83H truncation mutations causing ADHCAI in humans disturb amelogenesis through a neomorphic mechanism, rather than haploinsufficiency.

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Section: Discussionmentioning

confidence: 98%

The Enamel Phenotype in Homozygous Fam83h Truncation Mice

Wang

Smith

et al. 2019

Molec Gen & Gen Med

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“…FAM83A is involved in regulating a variety of different tumor-related signaling pathways, including the EGFR, RAS/RAF/MEK/ERK, and PI3K/AKT/mTOR pathways (3,4). The overexpression of FAM83A has been shown in lung, breast, testicular, and bladder cancers and is associated with promoting the development of cancers (7)(8)(9)(19)(20)(21)(22). Li et al (3) reported that FAM83A is highly expressed in lung cancer tissues, especially LUAD.…”

Section: Discussionmentioning

confidence: 99%

FAM83A Promotes Lung Cancer Progression by Regulating the Wnt and Hippo Signaling Pathways and Indicates Poor Prognosis

Zheng

Lei

et al. 2020

Front. Oncol.

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FAM83A (family with sequence similarity 83, member A) has been found to be highly expressed in cancers. The purpose of this study was to clarify the role and mechanism of FAM83A in lung cancers. The expression of FAM83A in lung cancer cells was enhanced by gene transfection or knocked down by small interfering RNA interference. The key proteins of the Wnt signaling pathway, the Hippo signaling pathway, and epithelial-mesenchymal transition (EMT) were examined using Western blot. The proliferation and invasion of lung cancer cells were examined using cell proliferation, colony formation, and invasion assays. The expression of FAM83A in lung cancer tissues was significantly increased and was correlated with advanced tumor-node-metastasis (TNM) stage and poor prognosis. Overexpression of FAM83A enhanced the proliferation, colony formation, and invasion of lung cancer cells. Meanwhile, FAM83A overexpression increased the expression of active β-catenin and Wnt target genes and the activity of EMT. Furthermore, in FAM83A-overexpressed cells, the activity of Hippo pathway was downregulated, whereas the expression of yes-associated protein (YAP) and its downstream targets cyclin E and CTGF were upregulated. The inhibitor of the Wnt signaling pathway, XAV-939, reversed the promoting effect of FAM83A on YAP, cyclin E, and CTGF. On knocking down the expression of FAM83A, we obtained the opposite results. However, the inhibitor of GSK3β, CHIR-99021, restored the expression of YAP, cyclin E, and CTGF after FAM83A was knocked down. FAM83A is highly expressed in lung cancers and correlated with advanced TNM stage and poor prognosis. FAM83A promotes the proliferation and invasion of lung cancer cells by regulating the Wnt and Hippo signaling pathways and EMT process.

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“…Il6st is in the royalblue module, along with transcripts that are significantly enriched for the GO term, "positive regulation of cytokine production". The FAM83 family consists of eight members, several of which are increased in expression or copy number in various cancers, and are downstream of the phosphatidylinositol 3-kinase and epidermal growth factor receptor pathways (SNIJDERS et al 2017). …”

Section: Discussionmentioning

confidence: 99%

Genetic Drivers of Pancreatic Islet Function

et al. 2018

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The majority of gene loci that have been associated with type 2 diabetes play a role in pancreatic islet function. To evaluate the role of islet gene expression in the etiology of diabetes, we sensitized a genetically diverse mouse population with a Western diet high in fat (45%-kcal) and sucrose (34%) and carried out genome-wide association mapping of diabetes-related phenotypes. We quantified mRNA abundance in the islets and identified 18,820 expression quantitative trait loci. We applied mediation analysis to identify candidate causal driver genes at loci that affect the abundance of numerous transcripts. These include two genes previously associated with monogenic diabetes (PDX1 and HNF4A), as well as three genes with nominal association with diabetes-related traits in humans (FAM83E, IL6ST, and SAT2). We grouped transcripts into gene modules and mapped regulatory loci for modules enriched with transcripts specific for α-cells, and another specific for δ-cells. However, no single module enriched for β-cell-specific transcripts, suggesting heterogeneity of gene expression patterns within the β-cell population. A module enriched in transcripts associated with branched chain amino acid metabolism was the most strongly correlated with physiological traits that reflect insulin resistance. Although the mice in this study were not overtly diabetic, the analysis of pancreatic islet gene expression under dietary-induced stress enabled us to identify correlated variation in groups of genes that are functionally linked to diabetes-associated physiological traits. Our analysis suggests an expected degree of concordance between diabetes-associated loci in the mouse with those found in human populations and demonstrates how the mouse can provide evidence to support nominal associations found in human genome-wide association mapping.4

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FAM83 family oncogenes are broadly involved in human cancers: an integrative multi‐omics approach

Cited by 98 publications

References 32 publications

The Enamel Phenotype in Homozygous Fam83h Truncation Mice

The Enamel Phenotype in Homozygous Fam83h Truncation Mice

FAM83A Promotes Lung Cancer Progression by Regulating the Wnt and Hippo Signaling Pathways and Indicates Poor Prognosis

Genetic Drivers of Pancreatic Islet Function

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