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

Yamaura, Takumi; Ezaki, Junji; Okabe, Naoyuki; Takagi, Hironori; Ozaki, Yuki; Inoue, Takuya; Watanabe, Yuzuru; Fukuhara, Mitsuro; Muto, Satoshi; Matsumura, Yuki; Hasegawa, T.; Hoshino, Mika; Osugi, Jun; Shio, Yutaka; Waguri, Satoshi; Tamura, Haruka; Imai, Jun‐ichi; Ito, Emi; Yanagisawa, Yuka; Honma, Reiko; Watanabe, Shinya; Suzuki, Hiroyuki

doi:10.3892/ol.2017.7517

Cited by 10 publications

(15 citation statements)

References 31 publications

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“…In addition to the evaluation of FAM83 expression in tumor tissue, functional assays were performed in several NSCLC cell lines. In agreement with previous studies, FAM83A and B depletion had a significant effect on the proliferation and AIG of ADC cells [8,9,27]. We were able to show that downregulation of FAM83A resulted in impaired migration.…”

Section: Discussionsupporting

confidence: 92%

“…Because of its involvement in PI3K/Akt and MAPK signaling, FAM83B has also been shown to confer a decreased sensitivity to PI3K, Akt, and mTOR inhibitors in immortalized human mammary epithelial cells [13]. In lung ADC, FAM83B expression has been shown to be significantly elevated in tumors with wild-type EGFR [27], while in our patient samples, a significant difference was not observed. Here again, differences in quantification methods might be responsible for the divergent results.…”

Section: Discussionmentioning

confidence: 74%

“…Here again, differences in quantification methods might be responsible for the divergent results. Moreover, the study from Yamaura et al only included Japanese patients [24,27]. Interestingly, our analysis of lung ADC patients revealed that FAM83A had lower expression in tumors with a mutant variant of EGFR.…”

Section: Discussionmentioning

confidence: 91%

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FAM83A and FAM83B as Prognostic Biomarkers and Potential New Therapeutic Targets in NSCLC

Richtmann

Wilkens

Warth

et al. 2019

Cancers

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Although targeted therapy has improved the survival rates in the last decade, non-small-cell lung cancer (NSCLC) is still the most common cause of cancer-related death. The challenge of identifying new targets for further effective therapies still remains. The FAMily with sequence similarity 83 (FAM83) members have recently been described as novel oncogenes in numerous human cancer specimens and shown to be involved in epidermal growth factor receptor (EGFR) signaling. Here, gene expression of FAM83A and B was analyzed in a cohort of 362 NSCLC patients using qPCR. We further investigated relations in expression and their prognostic value. Functional assays in NSCLC cell lines were performed to evaluate FAM83A and B involvement in proliferation, anchorage-independent growth, migration, and the EGFR pathway. We observed a highly increased gene expression level of FAM83A (ø = 68-fold) and FAM83B (ø = 20-fold) which resulted in poor survival prognosis (p < 0.0001 and p = 0.002). Their expression was influenced by EGFR levels, pathway signaling, and mutation status. Both genes affected cell proliferation, and FAM83A depletion resulted in reduced migration and anchorage-independent growth. The results support the hypothesis that FAM83A and B have different functions in different histological subtypes of NSCLC and might be new therapeutic targets.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 74%

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FAM83A and FAM83B as Prognostic Biomarkers and Potential New Therapeutic Targets in NSCLC

Richtmann

Wilkens

Warth

et al. 2019

Cancers

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“…To better elucidate the role of FAM83B in the maintenance of thyroid cell differentiation and in cell migration, we performed silencing experiments using two different siRNAs 11 in the two cell lines, NTHY-ORI and TPC1, which expressed high FAM83B levels. We found that the knock down of FAM83B significantly affect normal and tumor thyroid cell differentiation, inducing in NTHY-ORI a reduction in the expression of the thyroid marker genes PAX8 and NIS (Fig.…”

Section: Resultsmentioning

confidence: 99%

FAM83B is involved in thyroid cancer cell differentiation and migration

Cirello

Grassi

Pogliaghi

et al. 2022

Sci Rep

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FAM83B has been recently identified as an oncogene, but its role in thyroid cancers (TC) is still unclear. We examined the expression of FAM83B and its possible involvement in cell migration and differentiation, in neoplastic/normal thyroid tissues and in TC human cell lines. FAM83B expression in TC varies according to the tumor histotype, being significantly downregulated in more aggressive and metastatic tissues. FAM83B levels in cell lines recapitulate patients’ samples variations, and its total and cytoplasmic levels decrease upon the induction of migration, together with an increase in its nuclear localization. Similar variations were detected in the primary tumor and in the metastatic tissues from a follicular TC. FAM83B knock down experiments confirmed its role in thyroid differentiation and cell migration, as demonstrated by the reduction of markers of thyroid differentiation and the increase of the mesenchymal marker vimentin. Moreover, the silencing of FAM83B significantly increased cells migration abilities, while not affecting the oncogenic RAS/MAPK/PI3K pathways. Our data indicate for the first time a role for FAM83B in TC cell differentiation and migration. Its expression is reduced in dedifferentiated tumors and its nuclear re-localization could favour distant migration, suggesting that FAM83B should be considered a possible diagnostic and prognostic biomarker.

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“…Family with sequence similarity 83, member B ( FAM83B ) is reported to be a novel molecule involved in the development of various malignant tumors, including pancreatic ductal Adenocarcinoma ( 10 ) and gastric cancer ( 11 ). Previous studies have demonstrated that FAM83B can directly activate the PI3K/AKT/mTOR signaling pathway in tumors, including breast, lung, ovarian and cervical cancer, by binding to PI3K ( 12 , 13 ) or can indirectly activate the pathway by binding and hyper-activating EGFR in lung adenocarcinoma ( 14 ). Our previous study demonstrated that FAM83B knockdown inhibits endometrial cancer cell proliferation and metastasis through the inhibition of the PI3K/AKT/mTOR signaling pathway ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑199a/b‑5p inhibits endometrial cancer cell metastasis and invasion by targeting FAM83B in the epithelial‑to‑mesenchymal transition signaling pathway

et al. 2021

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Our previous study demonstrated the role of family with sequence similarity 83, member B (FAM83B) in endometrial cancer tumorigenesis and metastasis. FAM83B is involved in epithelial-to-mesenchymal transition (EMT). However, the regulatory network of EMT, which promotes endometrial cancer cell metastasis, involving microRNAs (miRNAs/miRs) and FAM83B, has not been elucidated. To investigate the potential mechanism underlying miR-199a/b-5p in endometrial cancer, the effect of miR-199a/b-5p and its targeted FAM83B gene on the biological behaviour of endometrial cancer cells was assessed. The Gene Expression Omnibus dataset analysis results revealed that the expression levels of 150 miRNAs in non-cancerous endometrial tissues were upregulated compared with those in endometrial cancer tissues. TargetScan predicted that the nucleotides 672-679 of FAM83B 3'-untranslated region (UTR) were the target sites of miR-199a/b-5p. The differentially expressed miRNAs were enriched in several Kyoto Encyclopedia of Genes and Genomes pathways. Reverse transcription-quantitative PCR analysis revealed that the expression levels of miR-199a/b-5p in the endometrial non-cancerous cell lines were significantly upregulated compared with those in the six endometrial cancer cell lines. miR-199a/b-5p inhibited the EMT signaling pathway by regulating the expression levels of E-cadherin, N-cadherin, Snail, α-smooth muscle actin, vimentin and Twist. This suggested that miR-199a/b-5p inhibited endometrial cancer cell proliferation and migration through the inhibition of the EMT signaling pathway. Furthermore, the nucleotides 672-679 of the FAM83B 3'-UTR were demonstrated to be the binding site of miR-199a/b-5p. These results suggested that miR-199a/b-5p inhibited endometrial cancer cell proliferation and metastasis by targeting the 3'-UTR of FAM83B, which is involved in the EMT signaling pathway.

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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

Cited by 10 publications

References 31 publications

FAM83A and FAM83B as Prognostic Biomarkers and Potential New Therapeutic Targets in NSCLC

FAM83A and FAM83B as Prognostic Biomarkers and Potential New Therapeutic Targets in NSCLC

FAM83B is involved in thyroid cancer cell differentiation and migration

MicroRNA‑199a/b‑5p inhibits endometrial cancer cell metastasis and invasion by targeting FAM83B in the epithelial‑to‑mesenchymal transition signaling pathway

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