Secreted frizzled-related protein 4 and its implications in cancer and apoptosis

Our plain-English summary of Secreted frizzled-related protein 4 and its implications in cancer and apoptosis, by S. Pohl, R. Scott, F. Arfuso, et al (Tumour Biology, 2015).

The study

• Authors: S. Pohl, R. Scott, F. Arfuso, V. Perumal, A. Dharmarajan
• Journal: Tumour Biology
• Published: 2015;36(1):143-52
• Type of article: Review
• Cited by: 40 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Secreted frizzled-related protein 4 (SFRP4) is a glycoprotein that acts as an antagonist of Wnt ligands, causing inhibition of the canonical Wnt signalling pathway. First noticed due to high expression levels during times of increased apoptosis, SFRP4 has been implicated in cell proliferation and differentiation and plays an important role in carcinogenesis. Many tumours such as endometrial, cervical, ovarian, prostate, bladder, colorectal, mesothelioma, pancreatic, renal, and oesophageal tumours are characterised by aberrant promoter hypermethylation, which causes variations in the expression level of SFRP4 when compared to normal cells. Combined experimental data appear to confirm the suggested role of SFRP4 as a local initiator of apoptosis; however, increased SFRP4 expression may not always correlate with an increase in apoptosis, possibly due to the complex interactions between different signalling pathways. SFRP4 can be explored for its use in novel therapeutic modalities as well as being a potential diagnostic biomarker.

In plain English

This article was a review, not a new study. The authors summarised earlier published research on secreted frizzled-related protein 4 (SFRP4). SFRP4 is a protein that blocks the canonical Wnt signalling pathway, which normally encourages cells to multiply and to avoid programmed cell death (apoptosis). The review covered studies of endometrial, cervical, ovarian, prostate, bladder, colorectal, pancreatic, kidney, oesophageal, brain and pituitary tumours, and mesothelioma. On mesothelioma, it described earlier studies reporting that SFRP4 was reduced in many mesothelioma cell lines. One cited study, by Lee and colleagues, found a chemical change to the gene that can switch it off (methylation) in 17 of 19 tumour tissue samples. Another, by He and colleagues, reported that restoring SFRP4 to certain mesothelioma cells induced apoptosis. The article did not discuss asbestos or other workplace or environmental exposures. The authors concluded that SFRP4 could be explored as a treatment and as a diagnostic marker. They noted conflicting reports, particularly in colon cancer, and that higher SFRP4 does not always go with more apoptosis.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published research on SFRP4 in cancer and apoptosis
• Who was studied: No new participants. The review drew on previously published studies of human tumour tissue, cancer cell lines and animals across many cancer types, including mesothelioma.
• Exposure: Not applicable. The topic was the SFRP4 protein and Wnt signalling. Asbestos and other workplace or environmental exposures were not discussed.
• Main results:
  • Cited earlier studies reported that SFRP4 was downregulated in numerous mesothelioma cell lines.
  • A cited study by Lee et al. found SFRP4 methylation in 89% (17 of 19) of mesothelium tumour tissue samples.
  • A cited study by He et al. in beta-catenin-deficient mesothelioma cell lines reported that restoring SFRP4 expression induced apoptosis and reduced Dishevelled and the apoptosis inhibitor survivin.
  • Cited RNA interference and expression studies reported that silencing SFRP4 promoted cell growth and inhibited apoptosis.
• The authors' conclusion: The authors concluded that SFRP4 can be explored for use in new treatments and as a potential diagnostic biomarker.
• Limitations the authors state:
  • The authors noted conflicting reports, particularly in colon cancer cells, where higher SFRP4 levels appeared to go with more cell proliferation and tumour progression.
  • The authors noted that higher SFRP4 expression may not always be accompanied by more apoptosis.
  • The authors noted inconsistent results across studies when comparing SFRP4 levels with beta-catenin levels.

Topics

Medical terms in this study, explained in our Lexicon: Apoptosis, Glycoprotein, Carcinogenesis, Mesothelioma, Biomarker.

Related studies

• Delivery of expression constructs of secreted frizzled-related protein 4 and its domains by chitosan-dextran sulfate nanoparticles enhances their expression and anti-cancer effects — V. Perumal, F. Arfuso, et al. (2018)
• A protein kinase Cdelta-dependent protein kinase D pathway modulates ERK1/2 and JNK1/2 phosphorylation and Bim-associated apoptosis by asbestos — S.A. Buder-Hoffmann, A. Shukla, et al. (2009)
• The Wnt regulator SFRP4 inhibits mesothelioma cell proliferation, migration, and antagonizes Wnt3a via its netrin-like domain — V. Perumal, A.M. Dharmarajan, et al. (2017)
• Aberrant promoter methylation of WIF-1 and SFRP1, 2, 4 genes in mesothelioma — H. Kohno, V.J. Amatya, et al. (2010)
• Potential role of ferritin heavy chain in oxidative stress and apoptosis in human mesothelial and mesothelioma cells: implications for asbestos-induced oncogenesis — W. Aung, S. Hasegawa, et al. (2007)
• Malignant mesothelioma resistance to apoptosis: recent discoveries and their implication for effective therapeutic strategies — F. Villanova, A. Procopio, et al. (2008)

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