Understanding the cellular roles of Fyn-related kinase (FRK): implications in cancer biology

Goel, Raghuveera Kumar; Lukong, Kiven Erique

doi:10.1007/s10555-016-9623-3

Cited by 52 publications

(67 citation statements)

References 88 publications

(200 reference statements)

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“…Therefore, the results detected that Fyn kinase expression suppresses tumor progression and metastasis (22). In agreement with these studies and based on the multifunctional role of Fyn in various cancer cells, it has been implied that in cancer cells like lung cancer, Fyn-related kinase led to cell growth, invasion, and colony formation of cells (23), while in some cancer cells, including colon, breast and hepatocyte cancer, the expression of Fyn kinase increased (24).…”

Section: Discussionsupporting

confidence: 76%

The Effect of Myricetin Flavonoid on the Expression of Fyn Gene in Melanoma Cells (A375)

Abdolmaleki¹,

Moghbelinejad²,

Ahmadpour-Yazdi³

2017

Biotech Health Sci

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Background: Malignant melanoma as one of the most common cancers is currently spreading worldwide. Regarding after-effect of advanced treatments, using natural products has attracted much attention. Flavonoids, polyphenol compounds rich in diet, are being considered for their therapeutic preventive features. Fyn gene, a member of the protein tyrosine kinase oncogene family, has become an important target for therapy goals.

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Section: Discussionsupporting

confidence: 76%

The Effect of Myricetin Flavonoid on the Expression of Fyn Gene in Melanoma Cells (A375)

Abdolmaleki¹,

Moghbelinejad²,

Ahmadpour-Yazdi³

2017

Biotech Health Sci

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“…FRK is a candidate tumor suppressor [15, 17, 34]. Aberrant methylation of CpG sites in the promoter region of tumor repressor genes is frequently observed in most cancers [35–37].…”

Section: Resultsmentioning

confidence: 99%

“…The role of FRK in human cancer is unclear; however some reports have shown that its expression is lost in breast cancers and that its re-expression suppresses breast tumor growth [17]. To understand the expression pattern of FRK in breast cancer, we examined the levels of the transcript and protein in a panel of 40 human breast cancer cell lines and 4 non-malignant mammary epithelial cell lines.…”

Section: Discussionmentioning

confidence: 99%

Repression of Fyn-related kinase in breast cancer cells is associated with promoter site-specific CpG methylation

et al. 2017

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The triple-negative breast cancer subtype is highly aggressive and has no defined therapeutic target. Fyn-related kinase (FRK) is a non-receptor tyrosine kinase, reported to be downregulated in breast cancer and gliomas, where it is suggested to have tumor suppressor activity. We examined the expression profile of FRK in a panel of 40 breast cancer cells representing all the major subtypes, as well as in 4 non-malignant mammary epithelial cell lines. We found that FRK expression was significantly repressed in a proportion of basal B breast cancer cell lines. We then determined the mechanism of suppression of FRK in FRK-low or negative cell lines. In silico analyses of the FRK promoter region led to the identification of at least 17 CpG sites. Bisulphite sequencing of the promoter region revealed that two of these sites were consistently methylated in FRK-low/negative cell lines and especially in the basal B breast cancer subtype. We further show that treatment of these cells with histone deacetylase inhibitors, Entinostat and Mocetinostat' promoted re-expression of FRK mRNA and protein. Further, using luciferase reporter assays, we show that both GATA3-binding protein FOG1 and constitutively active STAT5A increased the activity of FRK promoter. Together, our results present the first evidence that site-specific promoter methylation contributes to the repression of FRK more so in basal B breast cancers. Our study also highlights the potential clinical significance of targeting FRK using epigenetic drugs specifically in basal B breast cancers which are usually triple negative and very aggressive.

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“…In HepG2, we observed a partial LOH for the 5' portion FRK (Table S3). Since its discovery in 1993, FRK was first attributed as a tumor suppressor (Craven et al 1995;Oberg-Welsh et al 1998;Brauer and Tyner 2009;Kim et al 2015); however, further investigations show that FRK appears to play a tissue-specific oncogenic role in liver, pancreatic, breast and brain cancers and has been proposed as a therapeutic target (Goel and Lukong 2016). Interestingly, it was shown ectopic overexpression of FRK in HepG2 had no effect on cell proliferation, while this overexpression results in a significant growth reduction (p-value < 0.05) was observed in HepG2 cells with FRK-knockdown .…”

Section: Discussionmentioning

confidence: 99%

Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2

Zhou

Greer

Spies

et al. 2018

Preprint

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HepG2 is one of the most widely used human cell lines in biomedical research and one of the main cell lines of ENCODE. Although the functional genomic and epigenomic characteristics of HepG2 are extensively studied, its genome sequence has never been comprehensively analyzed and higher-order structural features of its genome beyond its karyotype were only cursorily known. The high degree of aneuploidy in HepG2 renders traditional genome variant analysis methods challenging and partially ineffective. Correct and complete interpretation of the extensive functional genomics data fromHepG2 requires an understanding of the cell line's genome sequence and genome structure. We performed deep whole-genome sequencing, mate-pair sequencing and linked-read sequencing to identify a wide spectrum of genome characteristics in HepG2: copy numbers of chromosomal segments, SNVs and Indels (both corrected for copynumber), phased haplotype blocks, structural variants (SVs) including complex genomic rearrangements, and novel mobile element insertions. A large number of SVs were phased, sequence assembled and experimentally validated. Several chromosomes show striking loss of heterozygosity. We re-analyzed HepG2 RNA-Seq and wholegenome bisulfite sequencing data for allele-specific expression and phased DNA methylation. We show examples where deeper insights into genomic regulatory complexity could be gained by taking knowledge of genomic structural contexts into account. Furthermore, we used the haplotype information to produce an allele-specific CRISPR targeting map. This comprehensive whole-genome analysis serves as a resource for future studies that utilize HepG2.

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Understanding the cellular roles of Fyn-related kinase (FRK): implications in cancer biology

Cited by 52 publications

References 88 publications

The Effect of Myricetin Flavonoid on the Expression of Fyn Gene in Melanoma Cells (A375)

The Effect of Myricetin Flavonoid on the Expression of Fyn Gene in Melanoma Cells (A375)

Repression of Fyn-related kinase in breast cancer cells is associated with promoter site-specific CpG methylation

Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2

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