Fascin actin-bundling protein 1 in human cancer: Promising biomarker or therapeutic target?

Liu, Hongliang; Zhang, Yu; Li, Li; Cao, Ji‐Min; Guo, Yujia; Wu, Yongyan; Gao, Wei

doi:10.1016/j.omto.2020.12.014

Cited by 60 publications

(68 citation statements)

References 271 publications

(444 reference statements)

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“…Among the DEGs shared within cell models, we could find some genes playing relevant roles for cytoskeleton dynamics, like Fscn1 (DEG in Saos-TetOn and MGCs) or Scd4 (DEG in Saos-TetOn and E14TG2α). FSCN1 is an actin binding-protein involved in the formation of essential cell structures for migration, cell-tocell interactions and cell-matrix adhesion (Lamb and Tootle, 2020); therefore, different studies have highlighted its importance for tissue architecture, particularly when it is disrupted in tumor microenvironments (Liu et al, 2021). Syndecans are transmembrane proteins which act as communicators between intracellular, cell surface and ECM components (Elfenbein and Simons, 2013).…”

Section: Tap73 As a Central Hub That Modulates Transcriptional Programs Involved In Cytoskeleton Dynamics And Cellular Adhesionmentioning

confidence: 99%

p73 as a Tissue Architect

Maeso‐Alonso

López-Ferreras

Marques

et al. 2021

Front. Cell Dev. Biol.

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The TP73 gene belongs to the p53 family comprised by p53, p63, and p73. In response to physiological and pathological signals these transcription factors regulate multiple molecular pathways which merge in an ensemble of interconnected networks, in which the control of cell proliferation and cell death occupies a prominent position. However, the complex phenotype of the Trp73 deficient mice has revealed that the biological relevance of this gene does not exclusively rely on its growth suppression effects, but it is also intertwined with other fundamental roles governing different aspects of tissue physiology. p73 function is essential for the organization and homeostasis of different complex microenvironments, like the neurogenic niche, which supports the neural progenitor cells and the ependyma, the male and female reproductive organs, the respiratory epithelium or the vascular network. We propose that all these, apparently unrelated, developmental roles, have a common denominator: p73 function as a tissue architect. Tissue architecture is defined by the nature and the integrity of its cellular and extracellular compartments, and it is based on proper adhesive cell-cell and cell-extracellular matrix interactions as well as the establishment of cellular polarity. In this work, we will review the current understanding of p73 role as a neurogenic niche architect through the regulation of cell adhesion, cytoskeleton dynamics and Planar Cell Polarity, and give a general overview of TAp73 as a hub modulator of these functions, whose alteration could impinge in many of the Trp73–/– phenotypes.

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Section: Tap73 As a Central Hub That Modulates Transcriptional Programs Involved In Cytoskeleton Dynamics And Cellular Adhesionmentioning

confidence: 99%

p73 as a Tissue Architect

Maeso‐Alonso

López-Ferreras

Marques

et al. 2021

Front. Cell Dev. Biol.

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“…Over the last 5 years, fascin-1 (FSCN1), a globular actin-binding protein, has emerged as an interesting novel biomarker for the most aggressive human carcinomas ( 3 ). Immunohistochemical studies have demonstrated that FSCN1 overexpression in the tumor correlates with a decreased OS and with different aspects of carcinoma invasiveness ( 3 – 7 ). Our previous findings have shown that FSCN1 is differentially expressed between normal adrenals and ACCs ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Circulating Fascin 1 as a Promising Prognostic Marker in Adrenocortical Cancer

et al. 2021

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Fascin-1 (FSCN1) is an actin-bundling protein associated with an invasive and aggressive phenotype of several solid carcinomas, as it is involved in cell cytoskeleton rearrangement and filopodia formation. Adrenocortical carcinoma (ACC) is a rare endocrine malignancy characterized by poor prognosis, particularly when metastatic at diagnosis. Radical resection is the only therapeutic option for ACC patients in addition to the adjuvant treatment with mitotane. Novel specific biomarkers suggestive of tumor progression to refine diagnosis and prognosis of patients with advanced ACC are urgently needed. ACC intratumoral FSCN1 has previously been suggested as a valid prognostic marker. In the present study, we identified FSCN1 in the bloodstream of a small cohort of ACC patients (n = 27), through a specific ELISA assay for human FSCN1. FSCN1 can be detected in the serum, and its circulating levels were evaluated in pre-surgery samples, which resulted to be significantly higher in ACC patients from stage I/II and stage III/IV compared with nontumoral healthy controls (HC, n = 4, FI: 5.5 ± 0.8, P<0.001, and 8.0 ± 0.5, P < 0.001 for stage I/II and stage III/IV group vs HC, respectively). In particular, FSCN1 levels were significantly higher in advanced stage versus stage I/II (22.8 ± 1.1 vs 15.8 ± 1.8 ng/ml, P < 0.005, respectively). Interestingly, circulating levels of pre-surgical FSCN1 can significantly predict tumor progression/recurrence (Log rank = 0.013), but not the overall survival (Log rank=0.317), in patients stratified in high/low PreS FSCN1. In conclusion, these findings—though very preliminary—suggest that circulating FSCN1 may represent a new minimally-invasive prognostic marker in advanced ACC, in particular when measured before surgery enables histological diagnosis.

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“…The actin cytoskeleton in metastatic cancer cells is frequently dysregulated to promote cell migration, invasion and metastatic dissemination. Fascin is a monomeric actin bundling protein upregulated in essentially all the metastatic carcinoma (1)(2)(3). Fascin crosslinks actin filaments into straight and stiff bundles through its positively charged actin-binding surfaces (1,4,5).…”

Section: Introductionmentioning

confidence: 99%

“…Fascin has emerged as an attractive target for the development of anti-metastasis therapeutics (7,(10)(11)(12)(13) for several reasons. First, in adult animals fascin expression is absent in most tissues with the exception of neuronal tissues (1)(2)(3). Second, fascin expression is highly upregulated in transformed cancer cells, especially in metastatic cancer and fascin plays a causative role in promoting cancer metastasis (1,2).…”

Section: Introductionmentioning

confidence: 99%

“…First, in adult animals fascin expression is absent in most tissues with the exception of neuronal tissues (1)(2)(3). Second, fascin expression is highly upregulated in transformed cancer cells, especially in metastatic cancer and fascin plays a causative role in promoting cancer metastasis (1,2). Third, adult mice with homozygous deletion of fascin appeared to be healthy and fertile (14), which suggested that inhibitors specifically targeting fascin would likely be well tolerated in cancer patients.…”

Section: Introductionmentioning

confidence: 99%

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The Actin Bundling Protein Fascin Promotes Lung Cancer Growth and Metastasis by Enhancing Glycolysis and PFKFB3 Expression

Lin

Wang

et al. 2021

Preprint

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Fascin is a pro-metastasis actin bundling protein upregulated in essentially all the metastatic carcinoma. It is believed that fascin promotes cancer cell migration and invasion by facilitating membrane protrusions such as filopodia and invadopodia. Aerobic glycolysis is a key feature of cancer metabolism that provides critical intermediate metabolites for tumor growth and cell proliferation. Here we report that fascin increase glycolysis in lung cancer to promote tumor growth and metastasis. Fascin promotes glycolytic flux by increasing the expression and activities of phosphofructose kinase 1 and 2 (PFK1 and 2). The glycolytic function of fascin depends on activation of YAP1 through its canonical actin bundling activity. Fascin promotes the binding of YAP1 to a TEAD1/4 binding motif located 30 bp upstream of the PFKFB3 transcription start site to activate its transcription. Our interrogation of the TCGA database suggest that the fascin-YAP1-PFKFB3 circuit is likely conserved across different types of cancer. We further showed that the glycolytic function of fascin is essential for promotion of lung cancer growth and metastasis. Importantly, pharmacological inhibitors of fascin could be used to suppress the YAP1-PFKFB3 signaling and inhibit glycolysis in cancer cell lines, organoid cultures and xenograft metastasis models. Taken together, our data reveal an important glycolytic role of fascin in lung cancer metabolism, and suggest that pharmacological inhibitors of fascin could be used to reprogram cancer metabolism in lung cancer and potentially other cancer with fascin upregulation.

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Fascin actin-bundling protein 1 in human cancer: Promising biomarker or therapeutic target?

Cited by 60 publications

References 271 publications

p73 as a Tissue Architect

p73 as a Tissue Architect

Circulating Fascin 1 as a Promising Prognostic Marker in Adrenocortical Cancer

The Actin Bundling Protein Fascin Promotes Lung Cancer Growth and Metastasis by Enhancing Glycolysis and PFKFB3 Expression

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