Clinical and Therapeutic Implications of Follistatin in Solid Tumours

Shi, Lei; Resaul, Jeyna; Owen, Sioned; Ye, Lin; Jiang, Wen Guo

doi:10.21873/cgp.20005

Cited by 39 publications

(43 citation statements)

References 111 publications

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“…It was not expressed in bone, liver or skin ( Figure 1A). This correlates well with gene expression data from the recent review by Shi et al (6). Table I.…”

Section: Fst Is Expressed In a Variety Of Normal Tissues Cancer Tissuessupporting

confidence: 89%

“…FST is a known transcription target of activin signalling (23) and acts as a negative feedback regulator, binding activin with high affinity to prevent its interaction with activin receptors and inhibiting its biological cellular functions (4,6). Due to this regulatory influence, follistatin has also been implicated in tumourigenesis in certain solid tumours (6).…”

Section: Discussionmentioning

confidence: 99%

“…Due to this regulatory influence, follistatin has also been implicated in tumourigenesis in certain solid tumours (6). Some studies have examined the role of activin in breast cancer, however, very little is known regarding the influence of follistatin in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

“…These three main FST isoforms can also be glycosylated to yield six further FST isoforms (6). FST288 and FST315 are differentially expressed in human tissues, but FST315 is the predominant isoform, whilst the FST288 isoform accounts for less than 5% of the encoded mRNA (6,7) .…”

mentioning

confidence: 99%

“…Activin has primarily been seen as an inhibitor of cellular proliferation, although certain cell populations seem to be stimulated by activin. Thus, the overall result of activin/FST action in cancer may be both context and cell type specific (3,6).…”

mentioning

confidence: 99%

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Increased Expression of Follistatin in Breast Cancer Reduces Invasiveness and Clinically Correlates with Better Survival

Zabkiewicz

Resaul

Hargest

et al. 2017

CGP

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Abstract. Background Follistatin (FST) is a secreted extracellular regulatory protein that binds activin and, with less affinity, related TGFβ superfamily members such as bone morphogenetic proteins (BMPs), preventing access to their receptors (1, 2). Originally thought to act on the pituitary to regulate FSH release, FST has subsequently been noted in many other tissues, in particular co-localising with activin resulting in autocrine and paracrine cellular regulation (1, 3). As an antagonist of activin, FST has diverse regulatory roles in embryogenesis, tissue differentiation and repair, gonadal function and inflammatory and immune processes (3, 4).Three major FST isoforms can be produced, namely FST288 (from splice variant mRNA precursor FST317), FST315 (from splice variant mRNA precursor FST344) and a third FST isoform, FST303, produced from the post-translational truncation of the FST315 C-terminus (5). These three main FST isoforms can also be glycosylated to yield six further FST isoforms (6). FST288 and FST315 are differentially expressed in human tissues, but FST315 is the predominant isoform, whilst the FST288 isoform accounts for less than 5% of the encoded mRNA (6, 7) .The FST/activin interaction has been implicated in tumour proliferation, angiogenesis and metastasis in several solid tumours (8-11). Activin has primarily been seen as an inhibitor of cellular proliferation, although certain cell populations seem to be stimulated by activin. Thus, the overall result of activin/FST action in cancer may be both context and cell type specific (3, 6).In the breast, FST is expressed in the normal mammary gland and in different breast proliferative diseases, with additional experimental evidence suggesting that FST can modulate the breast cancer cell cycle (3,(12)(13)(14). However, its role in breast cancer growth and metastasis is far from clear. In this study we demonstrated a clinical correlation between FST expression and survival in breast cancer, and that overexpression of FST in vitro reduces invasion of breast cancer cells. Patients and MethodsCell lines and patient tissue samples. Human breast cell lines MCF-7,MDA MB 231, ZR-751, BT 549 and BT-20 were obtained from and cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% foetal calf serum and antibiotics (PAA Laboratories Ltd., Somerset, UK). Cells were incubated at 37˚C in 5% CO 2 at 95% humidity.Breast cancer tissue and normal breast tissue samples were collected during surgery at the University Hospital of Wales. In total, 93 tumour samples and 30 normal breast tissue samples were obtained from patients who were enrolled in the study. The tissues obtained during surgery were snap-frozen in liquid nitrogen and stored at −80˚C.

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“…It was not expressed in bone, liver or skin ( Figure 1A). This correlates well with gene expression data from the recent review by Shi et al (6). Table I.…”

Section: Fst Is Expressed In a Variety Of Normal Tissues Cancer Tissuessupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Increased Expression of Follistatin in Breast Cancer Reduces Invasiveness and Clinically Correlates with Better Survival

Zabkiewicz

Resaul

Hargest

et al. 2017

CGP

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Integrative characterisation of secreted factors involved in intercellular communication between prostate epithelial or cancer cells and fibroblasts

Clark

Niranjan

et al. 2023

Molecular Oncology

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Reciprocal interactions between prostate cancer cells and carcinomaassociated fibroblasts (CAFs) mediate cancer development and progression; however, our understanding of the signalling pathways mediating these cellular interactions remains incomplete. To address this, we defined secretome changes upon co-culture of prostate epithelial or cancer cells with fibroblasts that mimic bi-directional communication in tumours. Using antibody arrays, we profiled conditioned media from mono-and cocultures of prostate fibroblasts, epithelial and cancer cells, identifying secreted proteins that are upregulated in co-culture compared to monoculture. Six of these (CXCL10, CXCL16, CXCL6, FST, PDGFAA, IL-17B) were functionally screened by siRNA knockdown in prostate cancer cell/fibroblast co-cultures, revealing a key role for follistatin (FST), a secreted glycoprotein that binds and bioneutralises specific members of the TGF-b superfamily, including activin A. Expression of FST by both cell types was required for the fibroblasts to enhance prostate cancer cell proliferation and migration, whereas FST knockdown in co-culture grafts decreased tumour growth in mouse xenografts. This study highlights the complexity of prostate cancer cell-fibroblast communication, demonstrates that co-culture secretomes cannot be predicted from individual cultures, and identifies FST as a tumour-microenvironment-derived secreted factor that represents a candidate therapeutic target.

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Contribution of organokines in the development of NAFLD/NASH associated hepatocellular carcinoma

Vachher

Bansal

Kumar

et al. 2022

J of Cellular Biochemistry

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Globally the incidence of hepatocellular carcinoma (HCC) is on an upsurge. Evidence is accumulating that liver disorders like nonalcoholic fatty liver disease (NAFLD) and its more progressive form nonalcoholic steatohepatitis (NASH) are associated with increased risk of developing HCC. NAFLD has a prevalence of about 25% and 50%–90% in obese population. With the growing burden of obesity epidemic worldwide, HCC presents a major healthcare burden. While cirrhosis is one of the major risk factors of HCC, available literature suggests that NAFLD/NASH associated HCC also develops in minimum or noncirrhotic livers. Therefore, there is an urgent need to understand the pathogenesis and risk factors associated with NAFLD and NASH related HCC that would help in early diagnosis and favorable prognosis of HCC secondary to NAFLD. Adipokines, hepatokines and myokines are factors secreted by adipocytes, hepatocytes and myocytes, respectively, playing essential roles in cellular homeostasis, energy balance and metabolism with autocrine, paracrine and endocrine effects. In this review, we endeavor to focus on the role of these organokines in the pathogenesis of NAFLD/NASH and its progression to HCC to augment the understanding of the factors stimulating hepatocytes to acquire a malignant phenotype. This shall aid in the development of novel therapeutic strategies and tools for early diagnosis of NAFLD/NASH and HCC.

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Clinical and Therapeutic Implications of Follistatin in Solid Tumours

Cited by 39 publications

References 111 publications

Increased Expression of Follistatin in Breast Cancer Reduces Invasiveness and Clinically Correlates with Better Survival

Increased Expression of Follistatin in Breast Cancer Reduces Invasiveness and Clinically Correlates with Better Survival

Integrative characterisation of secreted factors involved in intercellular communication between prostate epithelial or cancer cells and fibroblasts

Contribution of organokines in the development of NAFLD/NASH associated hepatocellular carcinoma

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