FSCN1 acts as a promising therapeutic target in the blockade of tumor cell motility: a review of its function, mechanism, and clinical significance

Li, Zhongxun; Shi, Jing; Zhang, Nannan; Zheng, Xian; Jin, Yukun; Wen, Shuxin; Hu, Wanglai; Wu, Yongyan; Gao, Wei

doi:10.7150/jca.67977

Cited by 20 publications

(19 citation statements)

References 167 publications

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“…FSCN1 is a 55 kDa globular protein that belongs to a unique family of actinbundling proteins. 63 In comparison with 42 normal epithelial tissues, FSCN1 was significantly elevated in 111 BCa tissues. 64 The expression of FSCN1 was significantly correlated to urothelial carcinoma recurrence.…”

Section: ■ Discussionmentioning

confidence: 94%

“…Besides, the levels of A2M, C9, CFH, C1QC, and C4BPA were higher in urine samples from BCa patients than nontumor controls and considered as invasively diagnosis markers. FSCN1 is a 55 kDa globular protein that belongs to a unique family of actin-bundling proteins . In comparison with 42 normal epithelial tissues, FSCN1 was significantly elevated in 111 BCa tissues .…”

Section: Discussionmentioning

confidence: 99%

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Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer

Chang,

Chen,

Yin

et al. 2024

J. Proteome Res.

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Bladder cancer (BCa) is the predominant malignancy of the urinary system. Herein, a comprehensive urine proteomic feature was initially established for the noninvasive diagnosis and recurrence monitoring of bladder cancer. 279 cases (63 primary BCa, 87 nontumor controls (NT), 73 relapsed BCa (BCR), and 56 nonrelapsed BCa (BCNR)) were collected to screen urinary protein biomarkers. 4761 and 3668 proteins were qualified and quantified by DDA and sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis in two discovery sets, respectively. Upregulated proteins were validated by multiple reaction monitoring (MRM) in two independent combined sets. Using the multi-support vector machine-recursive feature elimination (mSVM-RFE) algorithm, a model comprising 13 proteins exhibited good performance between BCa and NT with an AUC of 0.821 (95% CI: 0.675−0.967), 90.9% sensitivity (95% CI: 72.7−100%), and 73.3% specificity (95% CI: 53.3− 93.3%) in the diagnosis test set. Meanwhile, an 11-marker classifier significantly distinguished BCR from BCNR with 75.0% sensitivity (95% CI: 50.0−100%), 81.8% specificity (95% CI: 54.5−100%), and an AUC of 0.784 (95% CI: 0.609−0.959) in the test cohort for relapse surveillance. Notably, six proteins (SPR, AK1, CD2AP, ADGRF1, GMPS, and C8A) of 24 markers were newly reported. This paper reveals novel urinary protein biomarkers for BCa and offers new theoretical insights into the pathogenesis of bladder cancer (data identifier PXD044896).

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Section: ■ Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer

Chang,

Chen,

Yin

et al. 2024

J. Proteome Res.

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“…m6A methyltransferase METTL14 can catalyse m6A methylation modification on mRNA, while reading protein IGF2BP3 can recognize the modification and affect gene expression, thereby affecting gene expression. FSCN1 is closely related to cell motility, EMT, migration, inflammation and immunity and has been reported as a potential therapeutic target for various cancers 20–23 . Interestingly, FSCN1 was predicted to have multiple m6A modification sites on its mRNA sequence through a sequence‐based m6A modification site predictor (http://www.cuilab.cn/sramp/).…”

Section: Resultsmentioning

confidence: 99%

N6‐methyladenosine methylation on FSCN1 mediated by METTL14/IGF2BP3 contributes to human papillomavirus type 16‐infected cervical squamous cell carcinoma

Tian,

Huang,

Zhang

et al. 2024

Clin Exp Pharma Physio

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Human papillomavirus (HPV) infection has been reported to be associated with N6‐methyladenosine (m6A) modification in cancers. However, the underlying mechanism by which m6A methylation participates in HPV‐related cervical squamous cell carcinoma (CSCC) remains largely unclear. In this study, we observed that m6A regulators methyltransferase like protein (METTL14) and insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) were upregulated in HPV‐positive CSCC tissues and cell lines, and their high expression predicted poor prognosis for HPV‐infected CSCC patients. Cellular functional experiments verified that HPV16 oncogenes E6/E7 upregulated the expression of METTL14 and IGF2BP3 to promote cell proliferation and epithelial mesenchymal transition of CSCC cells. Next, we found that E6/E7 stabilized fascin actin‐bundling protein 1 (FSCN1) mRNA and elevated FSCN1 expression in CSCC cells through upregulating METTL14/IGF2BP3‐mediated m6A modification, and FSCN1 expression was also validated to be positively associated with worse outcomes of HPV‐positive CSCC patients. Finally, HPV16‐positive CSCC cell lines SiHa and CaSki were transfected with knockdown vector for E6/E7 or METTL14/IGF2BP3 and overexpressing vector for FSCN1, and functional verification experiments were performed through using MTT assay, flow cytometry, wound healing assay and tumour formation assay. Results indicated that knockdown of E6/E7 or METTL14/IGF2BP3 suppressed cell proliferation, migration and tumorigenesis, and accelerated cell apoptosis of HPV‐positive CSCC cells. Their tumour‐suppressive effects were abolished through overexpressing FSCN1. Overall, HPV E6/E7 advanced CSCC development through upregulating METTL14/IGF2BP3‐mediated FSCN1 m6A modification.

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“…FSCN1 has been shown to promote mesenchymal-like changes in tumor cells, and is a potential therapeutic target in melanoma and breast cancer [3,4]. It is also associate with increased BLCA progression and metastasis [5,6], although the speci c mechanisms have not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

FSCN1/METTL3/TLN1 axis promotes the malignant progression in bladder carcinoma

Sun

Liu

Wang

et al. 2022

Preprint

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Background The RNA-binding protein (RBP) played an important role in tumors. FSCN1 functioned as an oncogene in bladder carcinoma (BLCA). FSCN1 has not been reported as an RBP in BLCA. The mechanism by which FSCN1 promoted BLCA invasion and metastasis has remained unclear. Methods The FSCN1-bound RNAs in BLCA cell lines were identified using RIP-sequencing. The regulatory relationship between FSCN1 and METTL3 or TLN1 was verified by RNA immunoprecipitation (RIP), RNA pulldown assay, co-immunoprecipitation (Co-IP), western blotting, quantitative real-time PCR (qRT-PCR) and immunofluorescence. The metastatic abilities of the BCLA cells were evaluated by in vitro wound healing and transwell assays, as well as in vivo models. Results TLN1 protein levels were higher in BLCA tissues compared to the paired para-tumor tissues, whereas its mRNA expression was lower in the tumors. Mechanistically, FSCN1 bound to and upregulated METTL3, which in turn repressed TLN1 mRNA expression through the latter’s 3'UTR. In addition, FSCN1 bound to the CDS region of TLN1 mRNA and promoted its translation. Knocking down FSCN1, METTL3 and TLN1 individually had an inhibitory effect on the proliferation, invasion, migration and metastasis of BLCA cells. Conclusions FSCN1 functions as an RBP to promote proliferation, invasion and migration of BLCA cells. The FSCN1/METTL3/TLN1 axis is a potential therapeutic target for BLCA.

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FSCN1 acts as a promising therapeutic target in the blockade of tumor cell motility: a review of its function, mechanism, and clinical significance

Cited by 20 publications

References 167 publications

Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer

Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer

N6‐methyladenosine methylation on FSCN1 mediated by METTL14/IGF2BP3 contributes to human papillomavirus type 16‐infected cervical squamous cell carcinoma

FSCN1/METTL3/TLN1 axis promotes the malignant progression in bladder carcinoma

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