Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Kenneth MaieseEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101926


Background and Discovery of WISP1

Wnt-1 inducible signaling pathway protein 1 (WISP1) is an exciting target for the development of new treatments against acute and chronic disorders that may involve cellular metabolism as well as the nervous, musculoskeletal, cardiac, pulmonary, and vascular systems (Maiese 2014) (Fig. 1). WISP1 also is known as CCN4 and is a member of the CCN family of proteins. The CCN family of proteins consists of six secreted extracellular matrix-associated proteins and is defined by the first three members of the family that include cysteine-rich protein 61, connective tissue growth factor, and nephroblastoma overexpressed gene. Each family member has four cysteine-rich modular domains that include insulin-like growth factor-binding...
This is a preview of subscription content, log in to check access.



This research was supported by the following grants to Kenneth Maiese: American Diabetes Association, American Heart Association, NIH NIEHS, NIH NIA, NIH NINDS, and NIH ARRA.


  1. Cernea M, Tang W, Guan H, Yang K. Wisp1 mediates Bmp3-stimulated mesenchymal stem cell proliferation. J Mol Endocrinol. 2016;56(1):39–46.PubMedCrossRefGoogle Scholar
  2. Klinke II. DJ. Induction of Wnt-inducible signaling protein-1 correlates with invasive breast cancer oncogenesis and reduced type 1 cell-mediated cytotoxic immunity: a retrospective study. PLoS Comput Biol. 2014;10(1):e1003409.PubMedCrossRefGoogle Scholar
  3. Knoblich K, Wang HX, Sharma C, Fletcher AL, Turley SJ, Hemler ME. Tetraspanin TSPAN12 regulates tumor growth and metastasis and inhibits beta-catenin degradation. Cell Mol Life Sci. 2014;71(7):1305–14.PubMedCrossRefGoogle Scholar
  4. Lu S, Liu H, Lu L, Wan H, Lin Z, Qian K, Yao X, Chen Q, Liu W, Yan J, Liu Z. WISP1 overexpression promotes proliferation and migration of human vascular smooth muscle cells via AKT signaling pathway. Eur J Pharmacol. 2016;788:90–7.PubMedCrossRefGoogle Scholar
  5. Maeda A, Ono M, Holmbeck K, Li L, Kilts TM, Kram V, Noonan ML, Yoshioka Y, McNerny E, Tantillo M, Kohn D, Lyons KM, Robey PG, Young MF. WNT1 induced secreted protein-1 (WISP1): a novel regulator of bone turnover and Wnt signaling. J Biol Chem. 2015;290(22):14004–18.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Maiese K. Novel applications of trophic factors, Wnt and WISP for neuronal repair and regeneration in metabolic disease. Neural Regen Res. 2015;10(4):518–28.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Maiese K. Picking a bone with WISP1 (CCN4): new strategies against degenerative joint disease. J Transl Sci. 2016;1(3):83–5.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Maiese K. WISP1: clinical Insights for a Proliferative and Restorative Member of the CCN Family. Curr Neurovasc Res. 2014;11(4):378–89.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Maiese K, Li F, Chong ZZ, Shang YC. The Wnt signaling pathway: aging gracefully as a protectionist? Pharmacol Ther. 2008;118(1):58–81.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Mercer KE, Hennings L, Sharma N, Lai K, Cleves MA, Wynne RA, Badger TM, Ronis MJ. Alcohol consumption promotes diethylnitrosamine-induced hepatocarcinogenesis in male mice through activation of the Wnt/beta-catenin signaling pathway. Cancer Prev Res (Phila). 2014;7(7):675–85.CrossRefGoogle Scholar
  11. Murahovschi V, Pivovarova O, Ilkavets I, Dmitrieva RM, Docke S, Keyhani-Nejad F, Gogebakan O, Osterhoff M, Kemper M, Hornemann S, Markova M, Kloting N, Stockmann M, Weickert MO, Lamounier-Zepter V, Neuhaus P, Konradi A, Dooley S, von Loeffelholz C, Bluher M, Pfeiffer AF, Rudovich N. WISP1 is a novel adipokine linked to inflammation in obesity. Diabetes. 2015;64(3):856–66.PubMedCrossRefGoogle Scholar
  12. Ono M, Inkson CA, Sonn R, Kilts TM, de Castro LF, Maeda A, Fisher LW, Robey PG, Berendsen AD, Li L, McCartney-Francis N, Brown AC, Crawford NP, Molinolo A, Jain A, Fedarko NS, Young MF. WISP1/CCN4: a potential target for inhibiting prostate cancer growth and spread to bone. PLoS One. 2013;8(8):e71709.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Sahin Ersoy G, Altun Ensari T, Subas S, Giray B, Simsek EE, Cevik O. WISP1 is a novel adipokine linked to metabolic parameters in gestational diabetes mellitus. J Matern Fetal Neonatal Med. 2016;8:1–5.Google Scholar
  14. Saidak Z, Le Henaff C, Azzi S, Marty C, Marie PJ. Low dose PTH increases osteoblast activity via decreased Mef2c/Sost in senescent osteopenic mice. J Endocrinol. 2014;223(1):25–33.PubMedCrossRefGoogle Scholar
  15. Shang YC, Chong ZZ, Wang S, Maiese K. Tuberous sclerosis protein 2 (TSC2) modulates CCN4 cytoprotection during apoptotic amyloid toxicity in microglia. Curr Neurovasc Res. 2013;10(1):29–38.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Shanmugam P, Valente AJ, Prabhu SD, Venkatesan B, Yoshida T, Delafontaine P, Chandrasekar B. Angiotensin-II type 1 receptor and NOX2 mediate TCF/LEF and CREB dependent WISP1 induction and cardiomyocyte hypertrophy. J Mol Cell Cardiol. 2011;50(6):928–38.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Shao H, Cai L, Grichnik JM, Livingstone AS, Velazquez OC, Liu ZJ. Activation of Notch1 signaling in stromal fibroblasts inhibits melanoma growth by upregulating WISP-1. Oncogene. 2011;30(42):4316–26.PubMedCrossRefGoogle Scholar
  18. Wang S, Chong ZZ, Shang YC, Maiese K. WISP1 (CCN4) autoregulates its expression and nuclear trafficking of beta-catenin during oxidant stress with limited effects upon neuronal autophagy. Curr Neurovasc Res. 2012;9(2):89–99.CrossRefGoogle Scholar
  19. Yang ZH, Zheng R, Gao Y, Zhang Q, Zhang H. Abnormal gene expression and gene fusion in lung adenocarcinoma with high-throughput RNA sequencing. Cancer Gene Ther. 2014;21(2):74–82.PubMedCrossRefGoogle Scholar
  20. Zemans RL, McClendon J, Aschner Y, Briones N, Young SK, Lau LF, Kahn M, Downey GP. Role of beta-catenin-regulated CCN matricellular proteins in epithelial repair after inflammatory lung injury. Am J Physiol Lung Cell Mol Physiol. 2013;304(6):L415–27.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Cellular and Molecular SignalingNewarkUSA