Fascin promotes lung cancer growth and metastasis by enhancing glycolysis and PFKFB3 expression

Lin, Shengchen; Li, Yunzhan; Wang, Dezhen; Huang, Chongbiao; Marino, David; Bollt, Oana; Wu, Chaodong; Taylor, Matthew D.; Li, Wei; DeNicola, Gina M.; Hao, Jihui; Singh, Pankaj K.; Yang, Shung‐Haur

doi:10.1016/j.canlet.2021.07.025

Cited by 51 publications

(47 citation statements)

References 50 publications

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“…On the other hand, Fascin (FSCN1)—an actin filament bundling protein—was significantly overexpressed in SqCC tissue compared to the other cancer types. The overexpression of FSCN1 in NSCLC has been previously reported to be associated with tumor growth, migration, invasion, and metastasis [ 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Lung Cancer Types—A Pilot Study

Sugár

Bugyi

Tóth

et al. 2022

Cancers

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Lung cancer is the leading cause of tumor-related mortality, therefore significant effort is directed towards understanding molecular alterations occurring at the origin of the disease to improve current treatment options. The aim of our pilot-scale study was to carry out a detailed proteomic analysis of formalin-fixed paraffin-embedded tissue sections from patients with small cell or non-small cell lung cancer (adenocarcinoma, squamous cell carcinoma, and large cell carcinoma). Tissue surface digestion was performed on relatively small cancerous and tumor-adjacent normal regions and differentially expressed proteins were identified using label-free quantitative mass spectrometry and subsequent statistical analysis. Principal component analysis clearly distinguished cancerous and cancer adjacent normal samples, while the four lung cancer types investigated had distinct molecular profiles and gene set enrichment analysis revealed specific dysregulated biological processes as well. Furthermore, proteins with altered expression unique to a specific lung cancer type were identified and could be the targets of future studies.

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Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Lung Cancer Types—A Pilot Study

Sugár

Bugyi

Tóth

et al. 2022

Cancers

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“…Functionally, Fascin contributes to the migration and invasion of cancer cells and is thereby crucial for stability and formation of specialized protrusive structures, socalled invadopodia [63]. Transcriptional regulation of Fascin is heterogeneous between different cell types, tissues, and tumors [63,64]. We have previously shown that a single viral oncoprotein, Tax-1 of HTLV-1, is a potent inducer of Fascin in T-cells depending on classical NF-κB signaling [36,41].…”

Section: Discussionmentioning

confidence: 99%

Alternative NF-κB Signaling Discriminates Induction of the Tumor Marker Fascin by the Viral Oncoproteins Tax-1 and Tax-2 of Human T-Cell Leukemia Viruses

Heym

Mohr

Engelbrecht

et al. 2022

Cancers

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Transcriptional regulation of the actin-bundling protein and tumor marker Fascin is highly diverse depending on cell and tumor type. Previously, we discovered that the viral oncoprotein Tax-1 of human T-cell leukemia virus type 1 (HTLV-1) considerably enhances Fascin expression in T-cells, depending on classical NF-κB signaling. In this study, we asked if the non-oncogenic Tax-2 of the related HTLV-2 is still able to induce Fascin by using luciferase assays, immunoblot, and qPCR. We found that Tax-2 only slightly induces Fascin expression compared to Tax-1; however, both Tax-1 and Tax-2 comparably activated a 1.6 kb fragment in the human Fascin promoter including Tax-responsive elements. Furthermore, we identified a link between Tax-induced activity of the alternative NF-κB pathway and Fascin induction. While treatment with the second mitochondria-derived activator of caspases (SMAC)-mimetic AZD5582, a compound known to robustly activate alternative NF-κB signaling, did not induce Fascin, combination of AZD5582 with activation of classical NF-κB signaling by Tax-2 significantly induced Fascin expression. In conclusion, our data demonstrate that both classical and alternative NF-κB activity are necessary for strong Fascin induction by the viral Tax oncoproteins, thus, shedding new light on the regulation of Fascin in T-cells and during viral transformation.

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“…There is previous evidence in the literature of FSCN1 involvement in tumor metabolism. In lung cancer, FSCN1 promotes cancer growth and metastasis by enhancing glycolysis and PFKFB3 expression through YAP1 activation [ 36 ]. In the context of PIK3CA mutation or amplification, high expression of FSCN1 is associated with poor prognosis and radiotherapy response in cancer patients; mutant PIK3CA (E542K and E545K) can enhance glucose metabolism and cell proliferation in cancer cells [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

LYAR Promotes Colorectal Cancer Progression by Upregulating FSCN1 Expression and Fatty Acid Metabolism

Zhou

Gao

et al. 2021

Oxidative Medicine and Cellular Longevity

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Colorectal cancer (CRC) is a highly malignant tumor associated with poor prognosis, yet the molecular mechanisms are not fully understood. In this study, we showed that LYAR, a nucleolar protein, is expressed at a higher level in CRC tissue than in adjacent normal tissue and that LYAR expression is closely associated with distant CRC metastasis. LYAR not only significantly promotes the migration and invasion of CRC cells in vitro, but knockdown (KD) of LYAR in CRC cells also inhibits xenograft tumor metastasis in vivo. Microarray analysis of LYAR KD cells combined with a chromatin immunoprecipitation (ChIP) assay, gene reporter assay, and rescue experiment indicated that FSCN1 (encoding fascin actin-bundling protein 1 (Fascin-1)) serves as a novel key regulator of LYAR-promoted migration and invasion of CRC cells. Knockdown of FSCN1 significantly inhibits subcutaneous tumorigenesis of CRC cells and leads to the downregulation of FASN and SCD, genes encoding key enzymes in fatty acid synthesis. In summary, this study reveals a novel mechanism by which LYAR promotes tumor cell migration and invasion by upregulating FSCN1 expression and affecting fatty acid metabolism in CRC.

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Fascin promotes lung cancer growth and metastasis by enhancing glycolysis and PFKFB3 expression

Cited by 51 publications

References 50 publications

Proteomic Analysis of Lung Cancer Types—A Pilot Study

Proteomic Analysis of Lung Cancer Types—A Pilot Study

Alternative NF-κB Signaling Discriminates Induction of the Tumor Marker Fascin by the Viral Oncoproteins Tax-1 and Tax-2 of Human T-Cell Leukemia Viruses

LYAR Promotes Colorectal Cancer Progression by Upregulating FSCN1 Expression and Fatty Acid Metabolism

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