FAM83H is involved in the progression of hepatocellular carcinoma and is regulated by MYC

Abstract

Family with sequence similarity 83, member h (FAM83H) was identified, from a genome-wide search, as having the genetic etiology of human autosomal dominant hypocalcified amelogenesis imperfecta 1 . Thereafter, various mutations of FAM83H have been detected in amelogenesis imperfecta 1-5 and FAM83H-associated amelogenesis imperfecta is reported to be the most prevalent form of amelogenesis imperfecta 3,6 . Therefore, studies on FAM83H have typically been focused on tooth development. However, the cytoplasmic localization of FAM83H protein suggests that FAM83H might be involved in other cellular processes, including tumorigenesis 2, 5 . Increased expression of FAM83H in cancer tissue compared with normal tissue has been presented in recent microarray data 7 . In colorectal cancer, FAM83H contributes to the progression of cancer via regulating keratin cytoskeleton organization [8][9][10] . FAM83H overexpression along with aberrant localization of CK-1α could contribute to the progression of colorectal cancer through keratin cytoskeleton organization 8 . Another study showed that FAM83H could be an important molecule that can cause androgen independent prostate cancer progression 11 .

Expression of FAM83H and ZNF16 are associated with shorter survival of patients with gallbladder carcinoma

“…Therefore, using established targeted therapeutic molecules which block cellular proliferation and invasiveness might be beneficial in the treatment of gallbladder carcinoma patients with tumors with high expression of FAM83H/ZNF16. Especially, MYC and the Wnt/β-catenin pathway might be a potential therapeutic targets of gallbladder carcinomas with high expression of FAM83H/ZNF16 because MYC is a transcriptional regulator of FAM83H and FAM83H stabilizes βcatenin [5,6,28,29]. In addition, FAM83H is involved in the invasiveness of cancer cells through the EMT pathway in hepatocellular carcinoma and osteosarcoma [5,6].…”

“…Especially, MYC and the Wnt/β-catenin pathway might be a potential therapeutic targets of gallbladder carcinomas with high expression of FAM83H/ZNF16 because MYC is a transcriptional regulator of FAM83H and FAM83H stabilizes βcatenin [5,6,28,29]. In addition, FAM83H is involved in the invasiveness of cancer cells through the EMT pathway in hepatocellular carcinoma and osteosarcoma [5,6]. Therefore, EMT-associated receptor tyrosine kinase might be a potential therapeutic target of FAM83H-overexpressing cancers [30].…”

“…However, recent reports have shown various roles of FAM83H in both normal cells and cancer cells. In addition to the role of FAM83H in enamel formation in teeth, it is important in maintaining the intracellular actin filament framework and is involved in cancer progression [3][4][5][6]. Expression of FAM83H in cancer cells is elevated compared with normal cells, which suggests FAM83H plays a role in tumorigenesis [7].…”

“…Disruption of the actin filament network by deregulated FAM83H expression is thought to induce epithelial-to-mesenchymal transition (EMT) [3]. FAM83H-mediated stimulation of EMT accelerates cancer progression [5,6]. Moreover, FAM83H stimulates the proliferation of cancer cells by inducing cell cycle progression in conjunction with MYC and canonical Wnt pathways [5,6].…”

“…FAM83H-mediated stimulation of EMT accelerates cancer progression [5,6]. Moreover, FAM83H stimulates the proliferation of cancer cells by inducing cell cycle progression in conjunction with MYC and canonical Wnt pathways [5,6]. The oncogene MYC transcriptionally stimulates FAM83H expression, and consequently, FAM83H stabilizes β-catenin to activate the canonical Wnt pathway [5].…”