A novel potent tumour promoter aberrantly overexpressed in most human cancers

Abstract

The complexity and heterogeneity of tumours have hindered efforts to identify commonalities among different cancers. Furthermore, because we have limited information on the prevalence and nature of ubiquitous molecular events that occur in neoplasms, it is unfeasible to implement molecular-targeted cancer screening and prevention. Here, we found that the FEAT protein is overexpressed in most human cancers, but weakly expressed in normal tissues including the testis, brain, and liver. Transgenic mice that ectopically expressed FEAT in the thymus, spleen, liver, and lung spontaneously developed invasive malignant lymphoma (48%, 19/40) and lung-metastasizing liver cancer (hepatocellular carcinoma) (35%, 14/40) that models human hepatocarcinogenesis, indicating the FEAT protein potently drives tumorigenesis in vivo. Gene expression profiling suggested that FEAT drives receptor tyrosine kinase and hedgehog signalling pathways. These findings demonstrate that integrated efforts to identify FEAT-like ubiquitous oncoproteins are useful and may provide promising approaches for cost-effective cancer screening and prevention.

Integrative network analysis of nineteen brain regions identifies molecular signatures and networks underlying selective regional vulnerability to Alzheimer’s disease

“…The most significant TCG is METTL13 (methyltransferase like 13), which was correlated with sum of NFT density estimates in the superior parietal lobule (BM7-SPL) ( r  = 0.70, P value = 1.25 × 10 –8 ). The protein product encoded by this gene is the antiapoptotic protein FEAT, which is also aberrantly overexpressed in various human cancer tissues [37]. Among the list of the top trait correlated genes is AKT2 , which encodes a serine/threonine-protein kinase Akt.…”

Modifier variant of METTL13 suppresses human GAB1–associated profound deafness

“…In transgenic mice, Mettl13 ectopic overexpression can drive tumorigenesis in vivo (55). Moreover, gene expression profiling of NIH3T3 cells overexpressing METTL13 dysregulated the RTK and hedgehogsignaling pathways (55). Intriguingly, METTL13 is predicted to have methyltransferase activity, spermidine/spermine synthase activity, or ubiquinone synthase activity, but these functions of METLL13 have not been experimentally demonstrated (55).…”

“…However, it has low expression in normal tissues including the testis, brain, and liver (55). In transgenic mice, Mettl13 ectopic overexpression can drive tumorigenesis in vivo (55). Moreover, gene expression profiling of NIH3T3 cells overexpressing METTL13 dysregulated the RTK and hedgehogsignaling pathways (55).…”

“…METTL13 is a functionally uncharacterized protein that is overexpressed in some human cancers. However, it has low expression in normal tissues including the testis, brain, and liver (55). In transgenic mice, Mettl13 ectopic overexpression can drive tumorigenesis in vivo (55).…”

FEAT enhances INSL3 expression in testicular Leydig cells

“…Cancers develop from the dysregulation of genes involved in normal development and tissue homeostasis (Garraway & Lander, ; Hanahan & Weinberg, ; Vogelstein et al, ). We have previously found that f aint e xpression in normal tissues, a berrant overexpression in t umors (FEAT), the protein encoded by methyltransferase‐like 13 ( METTL13 ), potently drives tumorigenesis in transgenic mice (Takahashi et al, ). FEAT is aberrantly upregulated in most human cancers including colorectal, pancreatic, prostate, breast, ovary, thyroid, and non‐small‐cell lung cancers.…”