Abstract
FAM84B is a risk gene in breast and prostate cancers. Its upregulation is associated with poor prognosis of prostate cancer, breast cancer, and esophageal squamous cell carcinoma. FAM84B facilitates cancer cell proliferation and invasion in vitro, and xenograft growth in vivo. The FAM84B and Myc genes border a 1.2 Mb gene desert at 8q24.21. Co-amplification of both occurs in 20 cancer types. Mice deficient of a 430 Kb fragment within the 1.2 Mb gene desert have downregulated FAM84B and Myc expressions concurrent with reduced breast cancer growth. Intriguingly, Myc works in partnership with other oncogenes, including Ras. FAM84B shares similarities with the H-Ras-like suppressor (HRASLS) family over their typical LRAT (lecithin:retinal acyltransferase) domain. This domain contains a catalytic triad, H23, H35, and C113, which constitutes the phospholipase A1/2 and O-acyltransferase activities of HRASLS1-5. These enzymatic activities underlie their suppression of Ras. FAM84B conserves H23 and H35 but not C113 with both histidine residues residing within a highly conserved motif that FAM84B shares with HRASLS1-5. Deletion of this motif abolishes FAM84B oncogenic activities. These properties suggest a collaboration of FAM84B with Myc, consistent with the role of the gene desert in strengthening Myc functions. Here, we will discuss recent research on FAM84B-derived oncogenic potential.
Highlights
Amplification of the FAM84B gene and increases in its expression at the protein level occur in both preclinical lesions and esophageal squamous cell carcinomas (ESCC) [82,83]
RNA sequencing (RNA-seq) analysis revealed a large number of differentially expressed genes (DEGs) in DU145 FAM84B xenografts compared to DU145 empty vector (EV) tumors
It is an interesting scenario for FAM84B to facilitate Ras signaling via inhibiting the actions of the H-Ras-like suppressor (HRASLS) family, and thereby in part contributing to its collaboration with Myc
Summary
The unique feature of activities; its impact on tumorigenesis remained unknown until recently As the this gene desert is the existence of multiple By examination of chromatin interactions using chromosome conformation capture (3C)-based technologies, the prostate, breast, and colon cancer risk regions within the 8q24.21 gene desert display long-range physical interaction with the Myc locus in a tissue-specific manner [71,72]. These non-coding risk regions contain super-enhancer elements and TCF-4 (transcription factor 4). The interplay between PVT1 and Myc has been intensively studied and reviewed [15]
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