Genetic Alterations of TRAF Proteins in Human Cancers

Abstract

The tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family of cytoplasmic adaptor proteins regulate the signal transduction pathways of a variety of receptors, including the TNF-R superfamily, Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), and cytokine receptors. TRAF-dependent signaling pathways participate in a diverse array of important cellular processes, including the survival, proliferation, differentiation, and activation of different cell types. Many of these TRAF-dependent signaling pathways have been implicated in cancer pathogenesis. Here we analyze the current evidence of genetic alterations of TRAF molecules available from The Cancer Genome Atlas (TCGA) and the Catalog of Somatic Mutations in Cancer (COSMIC) as well as the published literature, including copy number variations and mutation landscape of TRAFs in various human cancers. Such analyses reveal that both gain- and loss-of-function genetic alterations of different TRAF proteins are commonly present in a number of human cancers. These include pancreatic cancer, meningioma, breast cancer, prostate cancer, lung cancer, liver cancer, head and neck cancer, stomach cancer, colon cancer, bladder cancer, uterine cancer, melanoma, sarcoma, and B cell malignancies, among others. Furthermore, we summarize the key in vivo and in vitro evidence that demonstrates the causal roles of genetic alterations of TRAF proteins in tumorigenesis within different cell types and organs. Taken together, the information presented in this review provides a rationale for the development of therapeutic strategies to manipulate TRAF proteins or TRAF-dependent signaling pathways in different human cancers by precision medicine.

Inhibitory Effect of β-Carotene on Helicobacter pylori-Induced TRAF Expression and Hyper-Proliferation in Gastric Epithelial Cells

“…Overexpression of TRAF1 is known to induce the development of gastric carcinogenesis [31,32]. In the present study, transfection of the dominant negative mutant TRAF1 gene inhibited H. pylori-induced hyper-proliferation in AGS cells.…”

FAS‐mediated apoptosis impairment in patients with ALPS/ALPS‐like phenotype carrying variants on CASP10 gene

“…Although the CASP10 Tyr446Cys variant is present in 1·6% of Caucasians, it has been shown to be less effective than WT CASP10 in transmitting apoptosis signal (Zhu et al , ) and therefore potentially involved in the development of clinical phenotype. Our patient with this mutation fitted the diagnostic criteria of ALPS with raised count of DNTs and B222+‐DNTs.…”

Pro-apoptotic functions of TRAF2 in p53-mediated apoptosis induced by cisplatin

“…Collectively, these observations support our working model that TRAF2 promotes cisplatin-induced apoptosis. Genetic alterations of TRAF2, including deletion, mutation and gene amplification, are found in various cancers (Zhu et al, 2018). In particular, the expression levels of TRAF2 are increased in prostate cancer, pancreatic cancer, lung cancer, and gastric cancer (Zhu et al, 2018).…”

“…Genetic alterations of TRAF2, including deletion, mutation and gene amplification, are found in various cancers (Zhu et al, 2018). In particular, the expression levels of TRAF2 are increased in prostate cancer, pancreatic cancer, lung cancer, and gastric cancer (Zhu et al, 2018). On the other hand, loss-of-function mutants of TRAF2 are observed in ovarian cancer, uterine cancer, and esophageal cancer (Zhu et al, 2018).…”