FAM83 proteins: Fostering new interactions to drive oncogenic signaling and therapeutic resistance

Bartel, Courtney A.; Parameswaran, Neetha; Cipriano, Rocky; Jackson, Mark W.

doi:10.18632/oncotarget.9544

Cited by 43 publications

(42 citation statements)

References 111 publications

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“…Interestingly, in breast cancer, FAM83B is expressed at higher levels in tumors without estrogen and progesterone receptors or human EGFR-2, compared with receptor-positive tumors ( 21 ). Furthermore, FAM83H , the paralog of FAM83B , is overexpressed in androgen independent-prostate cancer ( 22 ). These findings could indicate that FAM83B has an oncogenic role without aberrant signals from driver gene mutations or overexpressed hormone receptors.…”

Section: Discussionmentioning

confidence: 99%

“…Our knockdown study of FAM83B showed that its expression was associated with tumor proliferation in cell lines expressing high levels of FAM83B ; however, H1975 cells showed that knockdown of low levels of FAM83B also inhibited proliferation. Of all the FAM83 members, only FAM83H knockout mice, which live for only 2 weeks, have been reported, and FAM83H is proposed to play a role in the maintenance of cell homeostasis ( 22 , 28 ). Other FAM83 family members, including FAM83B , may also be required at certain levels, even in normal cells.…”

Section: Discussionmentioning

confidence: 99%

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Family with sequence similarity 83, memberï¿½B is a predictor of poor prognosis and a potential therapeutic target for lung adenocarcinoma expressing wild‑type epidermal growth factor receptor

et al. 2017

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Lung adenocarcinoma (ADC) patients with tumors that harbor no targetable driver gene mutation, such as epidermal growth factor receptor (EGFR) gene mutations, have unfavorable prognosis, and thus, novel therapeutic targets are required. Family with sequence similarity 83, member B (FAM83B) is a biomarker for squamous cell lung cancer. FAM83B has also recently been shown to serve an important role in the EGFR signaling pathway. In the present study, the molecular and clinical impact of FAM83B in lung ADC was investigated. Matched tumor and adjacent normal tissue samples were obtained from 216 patients who underwent complete lung resection for primary lung ADC and were examined for FAM83B expression using cDNA microarray analysis. The associations between FAM83B expression and clinicopathological parameters, including patient survival, were examined. FAM83B was highly expressed in tumors from males, smokers and in tumors with wild-type EGFR. Multivariate analyses further confirmed that wild-type EGFR tumors were significantly positively associated with FAM83B expression. In survival analysis, FAM83B expression was associated with poor outcomes in disease-free survival and overall survival, particularly when stratified against tumors with wild-type EGFR. Furthermore, FAM83B knockdown was performed to investigate its phenotypic effect on lung ADC cell lines. Gene silencing by FAM83B RNA interference induced growth suppression in the HLC-1 and H1975 lung ADC cell lines. FAM83B may be involved in lung ADC tumor proliferation and can be a predictor of poor survival. FAM83B is also a potential novel therapeutic target for ADC with wild-type EGFR.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Family with sequence similarity 83, memberï¿½B is a predictor of poor prognosis and a potential therapeutic target for lung adenocarcinoma expressing wild‑type epidermal growth factor receptor

et al. 2017

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“…Family with sequence similarity 83 (FAM83) oncogenes were discovered by two screens separately [6,7]. Recently, multiple studies have identified overexpressed or dysregulated FAM83 members in cancer [8]. Among the eight FAM83 family genes (FAM83A-H), the 434-amino acid FAM83A protein is the smallest one.…”

Section: Introductionmentioning

confidence: 99%

FAM83A is amplified and promotes tumorigenicity in non-small cell lung cancer via ERK and PI3K/Akt/mTOR pathways

Hu¹,

Wang²,

Wang³

et al. 2020

Int. J. Med. Sci.

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Family with sequence similarity 83A (FAM83A) is a newly-found over-expressed oncogene in several types of cancers and associates with poor prognosis. However, the role that FAM83A may play in the carcinogenesis of non-small cell lung cancer (NSCLC) still needs to be defined. The present study aimed to investigate the function of FAM83A in NSCLC progression and to investigate the possible mechanism. Analysis of Gene Expression Omnibus (GEO) database and rt-PCR showed up-regulated expression of FAM83A in NSCLC. GEO and the Cancer Genome Atlas (TCGA) data analysis revealed that high expression level of FAM83A in NSCLC was associated with poor prognosis. In vitro experiments showed that depleting FAM83A by siRNA/shRNA significantly inhibited cell proliferation and induced cell apoptosis. Cell motility was also retarded after silencing FAM83A, as demonstrated by Transwell assay. FAM83A depletion in A549 cells also inhibited subcutaneous tumor growth and lung metastasis in vivo. Western blotting showed that silencing FAM83A decreased the phosphorylation of ERK and PI3K/Akt/mTOR. On the other hand, overexpressing FAM83A in vitro enhanced cell proliferation and invasiveness, which was repressed by PI3K inhibitor and ERK inhibitor separately. Taken together, our study suggests that FAM83A promotes tumorigenesis of NSCLC at least partly via ERK and PI3K/Akt/mTOR pathways, making it a promising therapeutic target.

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“…They have oncogenic potential and are frequently upregulated in human tumours. 7,8 Fam83F has 500 amino acids and a molecular weight of 55 kDa. It is highly expressed in platelets, pancreas, the gastrointestinal tract and testis.…”

Section: Introductionmentioning

confidence: 99%

Fam83F induces p53 stabilisation and promotes its activity

et al. 2019

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p53 is one of the most important tumour suppressor proteins currently known. It is activated in response to DNA damage and this activation leads to proliferation arrest and cell death. The abundance and activity of p53 are tightly controlled and reductions in p53's activity can contribute to the development of cancer. Here, we show that Fam83F increases p53 protein levels by protein stabilisation. Fam83F interacts with p53 and decreases its ubiquitination and degradation. Overexpression of Fam83F also increases p53 activity in cell culture experiments and in zebrafish embryos. Downregulation of Fam83F increases cell proliferation in zebrafish xenografts. Fam83F expression is induced in response to DNA damage. Its downregulation decreases transcription of p53's target genes during the DNA damage response and increases cell proliferation and the colony forming ability of cells, identifying Fam83F as an important regulator of the DNA damage response. Fam83F also enhances migration of cells harbouring mutant p53 demonstrating that it can also activate mutant forms of p53.

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FAM83 proteins: Fostering new interactions to drive oncogenic signaling and therapeutic resistance

Cited by 43 publications

References 111 publications

Family with sequence similarity 83, memberï¿½B is a predictor of poor prognosis and a potential therapeutic target for lung adenocarcinoma expressing wild‑type epidermal growth factor receptor

Family with sequence similarity 83, memberï¿½B is a predictor of poor prognosis and a potential therapeutic target for lung adenocarcinoma expressing wild‑type epidermal growth factor receptor

FAM83A is amplified and promotes tumorigenicity in non-small cell lung cancer via ERK and PI3K/Akt/mTOR pathways

Fam83F induces p53 stabilisation and promotes its activity

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