Upregulated expression of FGF13/FHF2 mediates resistance to platinum drugs in cervical cancer cells

Okada, Tomoko; Murata, Kazuhiro; Hirose, Ryoma; Matsuda, Chie; Komatsu, Tsunehiko; Ikekita, Masahiko; Nakawatari, Miyako; Nakayama, Fumiaki; Wakatsuki, Masaru; Ohno, Tatsuya; Kato, Shingo; Imai, Takashi; Imamura, Toru

doi:10.1038/srep02899

Cited by 46 publications

(49 citation statements)

References 30 publications

(34 reference statements)

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“…FGF13 , FGF12 , and FGF18 are members of the fibroblast growth factor (FGF) family, which are involved in a variety of biological processes, including cell proliferation, tumor growth, and invasion. A recent study demonstrated that FGF13 plays a pivotal role in mediating the resistance to platinum drugs in cervical cancer cells[17]. Matrix metalloproteinases (MMPs) are suggested to be correlated with the metastatic ability of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Sequencing Reveals Key Pathways and Genes Associated with Cisplatin Resistance in Lung Adenocarcinoma A549 Cells

Fang

Zhang

et al. 2017

PLoS ONE

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Acquired resistance to cisplatin-based chemotherapy frequently occurs in patients with non-small cell lung cancer, and the underlying molecular mechanisms are not well understood. The aim of this study was to investigate whether a distinct gene expression pattern is associated with acquired resistance to cisplatin in human lung adenocarcinoma. Whole-transcriptome sequencing was performed to compare the genome-wide gene expression patterns of the human lung adenocarcinoma A549 cisplatin-resistant cell line A549/DDP with those of its progenitor cell line A549. A total of 1214 differentially expressed genes (DEGs) were identified, 656 of which were upregulated and 558 were downregulated. Functional annotation of the DEGs in the Kyoto Encyclopedia of Genes and Genomes database revealed that most of the identified genes were enriched in the PI3K/AKT, mitogen-activated protein kinase, actin cytoskeleton regulation, and focal adhesion pathways in A549/DDP cells. These results support previous studies demonstrating that the pathways regulating cell proliferation and invasion confer resistance to chemotherapy. Furthermore, the results proved that cell adhesion and cytoskeleton regulation is associated with cisplatin resistance in human lung cancer. Our study provides new promising biomarkers for lung cancer prognosis and potential therapeutic targets for lung cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Transcriptome Sequencing Reveals Key Pathways and Genes Associated with Cisplatin Resistance in Lung Adenocarcinoma A549 Cells

Fang

Zhang

et al. 2017

PLoS ONE

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“…Although our study highlights the impact of FGF13 1A, possible contributions of other FGF13 isoforms should not be disregarded. Indeed, some FGF13 isoforms have been associated with cisplatinum resistance (44). Moreover, in neurons, FGF13 1B regulates microtubule dynamics and facilitates cell migration (24).…”

Section: Fgf13 Depletion Augments Nucleolar Size and Increases Rrna Andmentioning

confidence: 99%

Regulatory module involving FGF13, miR-504, and p53 regulates ribosomal biogenesis and supports cancer cell survival

Bublik

Bursać

Sheffer

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The microRNA miR-504 targets TP53 mRNA encoding the p53 tumor suppressor. miR-504 resides within the fibroblast growth factor 13 (FGF13) gene, which is overexpressed in various cancers. We report that the FGF13 locus, comprising FGF13 and miR-504, is transcriptionally repressed by p53, defining an additional negative feedback loop in the p53 network. Furthermore, we show that FGF13 1A is a nucleolar protein that represses ribosomal RNA transcription and attenuates protein synthesis. Importantly, in cancer cells expressing high levels of FGF13, the depletion of FGF13 elicits increased proteostasis stress, associated with the accumulation of reactive oxygen species and apoptosis. Notably, stepwise neoplastic transformation is accompanied by a gradual increase in FGF13 expression and increased dependence on FGF13 for survival ("nononcogene addiction"). Moreover, FGF13 overexpression enables cells to cope more effectively with the stress elicited by oncogenic Ras protein. We propose that, in cells in which activated oncogenes drive excessive protein synthesis, FGF13 may favor survival by maintaining translation rates at a level compatible with the protein qualitycontrol capacity of the cell. Thus, FGF13 may serve as an enabler, allowing cancer cells to evade proteostasis stress triggered by oncogene activation.proteostasis | p53 | miR-504 | FGF13 | ribosomal biogenesis

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“…Decreased FGF13 mRNA levels were found in paratracheal lymph node metastases of lung adenocarcinoma compared to primary tumours . Overexpression of FGF13 is associated with shorter progression‐free survival in pancreatic cancer and poor outcome in cervical cancer . In addition, in vitro data suggests that FGF13 mediates drug resistance in HeLa cells .…”

mentioning

confidence: 99%

“…Overexpression of FGF13 is associated with shorter progression‐free survival in pancreatic cancer and poor outcome in cervical cancer . In addition, in vitro data suggests that FGF13 mediates drug resistance in HeLa cells . Finally, a search of the cBioPortal public database suggests that the expression level of FGF13 mRNA is altered in more than 30% of PCa …”

mentioning

confidence: 99%

“…17 In addition, in vitro data suggests that FGF13 mediates drug resistance in HeLa cells. 17 Finally, a search of the cBioPortal public database suggests that the expression level of FGF13 mRNA is altered in more than 30% of PCa. 18,19 This study evaluated the FGF13 expression pattern in human PCa and PCa cell lines at the mRNA and protein levels using qRT-PCR and immunohistochemistry (IHC), respectively, and correlated the expression levels with clinicopathological parameters.…”

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confidence: 99%

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Increased expression of fibroblast growth factor 13 in prostate cancer is associated with shortened time to biochemical recurrence after radical prostatectomy

Toriseva

Tuomala

et al. 2016

Intl Journal of Cancer

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Fibroblast growth factor homologous factors (FHFs) belong to the fibroblast growth factor (FGF) superfamily, which plays an important role in prostate cancer (PCa). Mining of public database suggests that FGF13 (FHF2) mRNA expression is altered in over 30% of PCa cases. This study examined the FGF13 expression pattern in human PCa specimens and evaluated its potential as a biomarker for patient outcome after radical prostatectomy (RP). Immunohistochemistry (IHC) showed that FGF13 was detectable in the majority of human PCa samples, and FGF13 IHC scores were higher in high-grade prostatic intraepithelial neoplasia, in primary PCa and in metastatic PCa than in benign prostatic tissue. There was a significant association between high cytoplasmic FGF13 staining and a risk of biochemical recurrence (BCR) after RP. This was also evident in the intermediate to high-risk patient groups. In contrast, positive nuclear FGF13 staining along with low cytoplasmic FGF13 group showed a decreased BCR risk. Multivariate regression analysis indicated that high cytoplasmic FGF13 staining was associated with BCR and that this could serve as an independent prognostic marker in PCa. Several PCa cell lines showed increased FGF13 expression at the mRNA and protein levels compared to the immortalized prostate epithelial cell line PNT1a. Analysis of co-labeled cells suggested a possible interaction of FGF13 with a-tubulin and the voltage-gated sodium channel proteins (Na V s/VGSCs). Our data indicate that, for PCa patients after RP, FGF13 serves as a potential novel prognostic marker that improves prediction of BCR-free survival, in particular if combined with other clinical parameters.Prostate cancer (PCa) is one of the most commonly diagnosed cancers in men, especially in developed countries. Globally, PCa is estimated to account for 15% of all cancers diagnosed in men and 6.6% of total male cancer mortality. 1

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Upregulated expression of FGF13/FHF2 mediates resistance to platinum drugs in cervical cancer cells

Cited by 46 publications

References 30 publications

Transcriptome Sequencing Reveals Key Pathways and Genes Associated with Cisplatin Resistance in Lung Adenocarcinoma A549 Cells

Transcriptome Sequencing Reveals Key Pathways and Genes Associated with Cisplatin Resistance in Lung Adenocarcinoma A549 Cells

Regulatory module involving FGF13, miR-504, and p53 regulates ribosomal biogenesis and supports cancer cell survival

Increased expression of fibroblast growth factor 13 in prostate cancer is associated with shortened time to biochemical recurrence after radical prostatectomy

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