CD146, a Novel Target of CD44-signaling, Suppresses Breast Tumor Cell Invasion

Overview

Journal Cell Commun Signal

Publisher Biomed Central

Specialties Biochemistry
Cell Biology

Date 2017 Nov 11

PMID 29121955

Citations 10

Authors

Allal Ouhtit

Mohammed E Abdraboh

Andrew D Hollenbach

Hatem Zayed

Madhwa H G Raj

Affiliations

Soon will be listed here.

Abstract

Background: We have previously validated three novel CD44-downstream positively regulated transcriptional targets, including Cortactin, Survivin and TGF-β2, and further characterized the players underlying their separate signaling pathways. In the present study, we identified CD146 as a potential novel target, negatively regulated by CD44. While the exact function of CD146 in breast cancer (BC) is not completely understood, substantial evidence from our work and others support the hypothesis that CD146 is a suppressor of breast tumor progression.

Methods: Therefore, using molecular and pharmacological approaches both in vitro and in breast tissues of human samples, the present study validated CD146 as a novel target of CD44-signaling suppressed during BC progression.

Results: Our results revealed that CD44 activation could cause a substantial decrease of CD146 expression with an equally notable converse effect upon CD44-siRNA inhibition. More interestingly, activation of CD44 decreased cellular CD146 and increased soluble CD146 through CD44-dependent activation of MMP.

Conclusion: Here, we provide a possible mechanism by which CD146 suppresses BC progression as a target of CD44-downstream signaling, regulating neovascularization and cancer cell motility.

Citing Articles

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CD146 promotes malignant progression of breast phyllodes tumor through suppressing DCBLD2 degradation and activating the AKT pathway.

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Pro- and anti-tumour activities of CD146/MCAM in breast cancer result from its heterogeneous expression and association with epithelial to mesenchymal transition.

Mannion A, Odell A, Baker S, Matthews L, Jones P, Cook G Front Cell Dev Biol. 2023; 11:1129015.

PMID: 37138793 PMC: 10150653. DOI: 10.3389/fcell.2023.1129015.

References

Ouhtit A, Madani S, Gupta I, Shanmuganathan S, Abdraboh M, Al-Riyami H . TGF-β2: A Novel Target of CD44-Promoted Breast Cancer Invasion. J Cancer. 2013; 4(7):566-72. PMC: 3753531. DOI: 10.7150/jca.6638. View

Kebir A, Harhouri K, Guillet B, Liu J, Foucault-Bertaud A, Lamy E . CD146 short isoform increases the proangiogenic potential of endothelial progenitor cells in vitro and in vivo. Circ Res. 2010; 107(1):66-75. DOI: 10.1161/CIRCRESAHA.109.213827. View

Li G, Satyamoorthy K, Herlyn M . Dynamics of cell interactions and communications during melanoma development. Crit Rev Oral Biol Med. 2002; 13(1):62-70. DOI: 10.1177/154411130201300107. View

Fang X, Jiang H, Zhao X, Jiang W . The role of a new CD44st in increasing the invasion capability of the human breast cancer cell line MCF-7. BMC Cancer. 2011; 11:290. PMC: 3161032. DOI: 10.1186/1471-2407-11-290. View

Zabouo G, Imbert A, Jacquemier J, Finetti P, Moreau T, Esterni B . CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines. Breast Cancer Res. 2009; 11(1):R1. PMC: 2687703. DOI: 10.1186/bcr2215. View

Bauvois B . New facets of matrix metalloproteinases MMP-2 and MMP-9 as cell surface transducers: outside-in signaling and relationship to tumor progression. Biochim Biophys Acta. 2011; 1825(1):29-36. DOI: 10.1016/j.bbcan.2011.10.001. View

Wu G, Fu P, Chiang C, Huss W, Greenberg N, Wu M . Increased expression of MUC18 correlates with the metastatic progression of mouse prostate adenocarcinoma in the TRAMP model. J Urol. 2005; 173(5):1778-83. DOI: 10.1097/01.ju.0000154643.30048.2c. View

Johnson J, Rothbacher U, Sers C . The progression associated antigen MUC18: a unique member of the immunoglobulin supergene family. Melanoma Res. 1993; 3(5):337-40. DOI: 10.1097/00008390-199310000-00006. View

Harhouri K, Kebir A, Guillet B, Foucault-Bertaud A, Voytenko S, Piercecchi-Marti M . Soluble CD146 displays angiogenic properties and promotes neovascularization in experimental hind-limb ischemia. Blood. 2010; 115(18):3843-51. DOI: 10.1182/blood-2009-06-229591. View

10.

Bardin N, Anfosso F, Masse J, Cramer E, Sabatier F, Le Bivic A . Identification of CD146 as a component of the endothelial junction involved in the control of cell-cell cohesion. Blood. 2001; 98(13):3677-84. DOI: 10.1182/blood.v98.13.3677. View

11.

Johnson J . Cell adhesion molecules in the development and progression of malignant melanoma. Cancer Metastasis Rev. 2000; 18(3):345-57. DOI: 10.1023/a:1006304806799. View

12.

Ouhtit A, Gaur R, Abd Elmageed Z, Fernando A, Thouta R, Trappey A . Towards understanding the mode of action of the multifaceted cell adhesion receptor CD146. Biochim Biophys Acta. 2009; 1795(2):130-6. DOI: 10.1016/j.bbcan.2009.01.002. View

13.

Garcia S, Dales J, Charafe-Jauffret E, Carpentier-Meunier S, Andrac-Meyer L, Jacquemier J . Poor prognosis in breast carcinomas correlates with increased expression of targetable CD146 and c-Met and with proteomic basal-like phenotype. Hum Pathol. 2007; 38(6):830-41. DOI: 10.1016/j.humpath.2006.11.015. View

14.

Bretscher A, Edwards K, Fehon R . ERM proteins and merlin: integrators at the cell cortex. Nat Rev Mol Cell Biol. 2002; 3(8):586-99. DOI: 10.1038/nrm882. View

15.

Lin Y, Wu X, Shen Y, Bu P, Yang D, Yan X . A novel antibody AA98 V(H)/L directed against CD146 efficiently inhibits angiogenesis. Anticancer Res. 2008; 27(6B):4219-24. View

16.

Luca M, Hunt B, Bucana C, Johnson J, Fidler I, Bar-Eli M . Direct correlation between MUC18 expression and metastatic potential of human melanoma cells. Melanoma Res. 1993; 3(1):35-41. DOI: 10.1097/00008390-199304000-00006. View

17.

Mostert B, Kraan J, Vries J, van der Spoel P, Sieuwerts A, Schutte M . Detection of circulating tumor cells in breast cancer may improve through enrichment with anti-CD146. Breast Cancer Res Treat. 2010; 127(1):33-41. DOI: 10.1007/s10549-010-0879-y. View

18.

Satyamoorthy K, Muyrers J, Meier F, Patel D, Herlyn M . Mel-CAM-specific genetic suppressor elements inhibit melanoma growth and invasion through loss of gap junctional communication. Oncogene. 2001; 20(34):4676-84. DOI: 10.1038/sj.onc.1204616. View

19.

Wu G, Varma V, Wu M, Wang S, Qu P, Yang H . Expression of a human cell adhesion molecule, MUC18, in prostate cancer cell lines and tissues. Prostate. 2001; 48(4):305-15. DOI: 10.1002/pros.1111. View

20.

Ouhtit A, Abd Elmageed Z, Abdraboh M, Lioe T, Raj M . In vivo evidence for the role of CD44s in promoting breast cancer metastasis to the liver. Am J Pathol. 2007; 171(6):2033-9. PMC: 2111125. DOI: 10.2353/ajpath.2007.070535. View