The Role of Decorin and Biglycan Signaling in Tumorigenesis

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Dec 17

PMID 34917515

Citations 28

Authors

Valentina Diehl

Lisa Sophie Huber

Jonel Trebicka

Malgorzata Wygrecka

Renato V Iozzo

Liliana Schaefer

Affiliations

Soon will be listed here.

Abstract

The complex and adaptive nature of malignant neoplasm constitute a major challenge for the development of effective anti-oncogenic therapies. Emerging evidence has uncovered the pivotal functions exerted by the small leucine-rich proteoglycans, decorin and biglycan, in affecting tumor growth and progression. In their soluble forms, decorin and biglycan act as powerful signaling molecules. By receptor-mediated signal transduction, both proteoglycans modulate key processes vital for tumor initiation and progression, such as autophagy, inflammation, cell-cycle, apoptosis, and angiogenesis. Despite of their structural homology, these two proteoglycans interact with distinct cell surface receptors and thus modulate distinct signaling pathways that ultimately affect cancer development. In this review, we summarize growing evidence for the complex roles of decorin and biglycan signaling in tumor biology and address potential novel therapeutic implications.

Citing Articles

Comprehensive investigation of proteoglycan gene expression in breast cancer: Discovery of a unique proteoglycan gene signature linked to the malignant phenotype.

Buraschi S, Pascal G, Liberatore F, Iozzo R Proteoglycan Res. 2025; 3(1).

PMID: 40066261 PMC: 11893098. DOI: 10.1002/pgr2.70014.

Decorin: matrix-based pan-cancer tumor suppressor.

Appunni S, Saxena A, Ramamoorthy V, Zhang Y, Doke M, Nair S Mol Cell Biochem. 2025; .

PMID: 39954173 DOI: 10.1007/s11010-025-05224-z.

Extracellular matrix and pregnancy: functions and opportunities caught in the net.

Rossi F, Luppi S, Fejza A, Giolo E, Ricci G, Andreuzzi E Reprod Biol Endocrinol. 2025; 23(1):24.

PMID: 39953593 PMC: 11827249. DOI: 10.1186/s12958-025-01348-5.

Biglycan-driven risk stratification in ZFTA-RELA fusion supratentorial ependymomas through transcriptome profiling.

Okonechnikov K, Ghasemi D, Schrimpf D, Tonn S, Mynarek M, Koster J Acta Neuropathol Commun. 2025; 13(1):4.

PMID: 39762990 PMC: 11706152. DOI: 10.1186/s40478-024-01921-w.

Biglycan promotes tumour proliferation and invasion in human colon cancers.

Lu B, Zhu Y, Li G, Xu Y, Wen C, Ye W J Int Med Res. 2024; 52(11):3000605241300067.

PMID: 39612315 PMC: 11607748. DOI: 10.1177/03000605241300067.

References

Hibino S, Kawazoe T, Kasahara H, Itoh S, Ishimoto T, Sakata-Yanagimoto M . Inflammation-Induced Tumorigenesis and Metastasis. Int J Mol Sci. 2021; 22(11). PMC: 8196678. DOI: 10.3390/ijms22115421. View

Xu W, Neill T, Yang Y, Hu Z, Cleveland E, Wu Y . The systemic delivery of an oncolytic adenovirus expressing decorin inhibits bone metastasis in a mouse model of human prostate cancer. Gene Ther. 2014; 22(3):247-56. PMC: 4361227. DOI: 10.1038/gt.2014.110. View

CSORDAS G, Santra M, Reed C, Eichstetter I, McQuillan D, Gross D . Sustained down-regulation of the epidermal growth factor receptor by decorin. A mechanism for controlling tumor growth in vivo. J Biol Chem. 2000; 275(42):32879-87. DOI: 10.1074/jbc.M005609200. View

Renaude E, Kroemer M, Loyon R, Binda D, Borg C, Guittaut M . The Fate of Th17 Cells is Shaped by Epigenetic Modifications and Remodeled by the Tumor Microenvironment. Int J Mol Sci. 2020; 21(5). PMC: 7084267. DOI: 10.3390/ijms21051673. View

Hinshaw D, Shevde L . The Tumor Microenvironment Innately Modulates Cancer Progression. Cancer Res. 2019; 79(18):4557-4566. PMC: 6744958. DOI: 10.1158/0008-5472.CAN-18-3962. View

Ma H, Hueng D, Shui H, Han J, Wang C, Lai Y . Intratumoral decorin gene delivery by AAV vector inhibits brain glioblastomas and prolongs survival of animals by inducing cell differentiation. Int J Mol Sci. 2014; 15(3):4393-414. PMC: 3975403. DOI: 10.3390/ijms15034393. View

Mainz L, Rosenfeldt M . Autophagy and cancer - insights from mouse models. FEBS J. 2017; 285(5):792-808. DOI: 10.1111/febs.14274. View

Merline R, Schaefer R, Schaefer L . The matricellular functions of small leucine-rich proteoglycans (SLRPs). J Cell Commun Signal. 2009; 3(3-4):323-35. PMC: 2778586. DOI: 10.1007/s12079-009-0066-2. View

Jarvelainen H, Sainio A, Wight T . Pivotal role for decorin in angiogenesis. Matrix Biol. 2015; 43:15-26. PMC: 4560244. DOI: 10.1016/j.matbio.2015.01.023. View

10.

Schaefer L, Iozzo R . Biological functions of the small leucine-rich proteoglycans: from genetics to signal transduction. J Biol Chem. 2008; 283(31):21305-9. PMC: 2490788. DOI: 10.1074/jbc.R800020200. View

11.

Neill T, Chen C, Buraschi S, Iozzo R . Catabolic degradation of endothelial VEGFA via autophagy. J Biol Chem. 2020; 295(18):6064-6079. PMC: 7196639. DOI: 10.1074/jbc.RA120.012593. View

12.

Schulz M, Diehl V, Trebicka J, Wygrecka M, Schaefer L . Biglycan: A regulator of hepatorenal inflammation and autophagy. Matrix Biol. 2021; 100-101:150-161. DOI: 10.1016/j.matbio.2021.06.001. View

13.

Goyal A, Neill T, Owens R, Schaefer L, Iozzo R . Decorin activates AMPK, an energy sensor kinase, to induce autophagy in endothelial cells. Matrix Biol. 2014; 34:46-54. PMC: 4080419. DOI: 10.1016/j.matbio.2013.12.011. View

14.

Shatz M, Menendez D, Resnick M . The human TLR innate immune gene family is differentially influenced by DNA stress and p53 status in cancer cells. Cancer Res. 2012; 72(16):3948-57. PMC: 3443562. DOI: 10.1158/0008-5472.CAN-11-4134. View

15.

Schultze J, Cardoso A, Freeman G, Seamon M, Daley J, Pinkus G . Follicular lymphomas can be induced to present alloantigen efficiently: a conceptual model to improve their tumor immunogenicity. Proc Natl Acad Sci U S A. 1995; 92(18):8200-4. PMC: 41124. DOI: 10.1073/pnas.92.18.8200. View

16.

Neill T, Jones H, Crane-Smith Z, Owens R, Schaefer L, Iozzo R . Decorin induces rapid secretion of thrombospondin-1 in basal breast carcinoma cells via inhibition of Ras homolog gene family, member A/Rho-associated coiled-coil containing protein kinase 1. FEBS J. 2013; 280(10):2353-68. PMC: 3648593. DOI: 10.1111/febs.12148. View

17.

Lai A, Abella J, Park M . Crosstalk in Met receptor oncogenesis. Trends Cell Biol. 2009; 19(10):542-51. DOI: 10.1016/j.tcb.2009.07.002. View

18.

Picoli C, Goncalves B, Santos G, Rocha B, Costa A, Resende R . Pericytes cross-talks within the tumor microenvironment. Biochim Biophys Acta Rev Cancer. 2021; 1876(2):188608. DOI: 10.1016/j.bbcan.2021.188608. View

19.

Cianfanelli V, Fuoco C, Lorente M, Salazar M, Quondamatteo F, Gherardini P . AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation. Nat Cell Biol. 2014; 17(1):20-30. PMC: 4976803. DOI: 10.1038/ncb3072. View

20.

Li F, Sethi G . Targeting transcription factor NF-kappaB to overcome chemoresistance and radioresistance in cancer therapy. Biochim Biophys Acta. 2010; 1805(2):167-80. DOI: 10.1016/j.bbcan.2010.01.002. View