CD44 Glycosylation As a Therapeutic Target in Oncology

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Aug 8

PMID 35936713

Authors

Chengcheng Liao

Qian Wang

Jiaxing An

Jie Chen

Xiaolan Li

Qian Long

Linlin Xiao

Xiaoyan Guan

Jianguo Liu

Affiliations

Soon will be listed here.

Abstract

The interaction of non-kinase transmembrane glycoprotein CD44 with ligands including hyaluronic acid (HA) is closely related to the occurrence and development of tumors. Changes in CD44 glycosylation can regulate its binding to HA, Siglec-15, fibronectin, TM4SF5, PRG4, FGF2, collagen and podoplanin and activate or inhibit c-Src/STAT3/Twist1/Bmi1, PI3K/AKT/mTOR, ERK/NF-κB/NANOG and other signaling pathways, thereby having a profound impact on the tumor microenvironment and tumor cell fate. However, the glycosylation of CD44 is complex and largely unknown, and the current understanding of how CD44 glycosylation affects tumors is limited. These issues must be addressed before targeted CD44 glycosylation can be applied to treat human cancers.

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References

Faassen A, Schrager J, Klein D, Oegema T, Couchman J, McCarthy J . A cell surface chondroitin sulfate proteoglycan, immunologically related to CD44, is involved in type I collagen-mediated melanoma cell motility and invasion. J Cell Biol. 1992; 116(2):521-31. PMC: 2289300. DOI: 10.1083/jcb.116.2.521. View

Costa A, Campos D, Reis C, Gomes C . Targeting Glycosylation: A New Road for Cancer Drug Discovery. Trends Cancer. 2020; 6(9):757-766. DOI: 10.1016/j.trecan.2020.04.002. View

Amodio N, Di Martino M, Foresta U, Leone E, Lionetti M, Leotta M . miR-29b sensitizes multiple myeloma cells to bortezomib-induced apoptosis through the activation of a feedback loop with the transcription factor Sp1. Cell Death Dis. 2012; 3:e436. PMC: 3542610. DOI: 10.1038/cddis.2012.175. View

Lesley J, Hascall V, Tammi M, HYMAN R . Hyaluronan binding by cell surface CD44. J Biol Chem. 2000; 275(35):26967-75. DOI: 10.1074/jbc.M002527200. View

Faller C, Guvench O . Terminal sialic acids on CD44 N-glycans can block hyaluronan binding by forming competing intramolecular contacts with arginine sidechains. Proteins. 2014; 82(11):3079-89. PMC: 4206607. DOI: 10.1002/prot.24668. View

Vizcaino C, Mansilla S, Portugal J . Sp1 transcription factor: A long-standing target in cancer chemotherapy. Pharmacol Ther. 2015; 152:111-24. DOI: 10.1016/j.pharmthera.2015.05.008. View

Henke C, Roongta U, Mickelson D, Knutson J, McCarthy J . CD44-related chondroitin sulfate proteoglycan, a cell surface receptor implicated with tumor cell invasion, mediates endothelial cell migration on fibrinogen and invasion into a fibrin matrix. J Clin Invest. 1996; 97(11):2541-52. PMC: 507340. DOI: 10.1172/JCI118702. View

Ogura K, Nagata K, Hatanaka H, Habuchi H, Kimata K, Tate S . Solution structure of human acidic fibroblast growth factor and interaction with heparin-derived hexasaccharide. J Biomol NMR. 1999; 13(1):11-24. DOI: 10.1023/a:1008330622467. View

Pachon-Pena G, Donnelly C, Ruiz-Canada C, Katz A, Fernandez-Veledo S, Vendrell J . A Glycovariant of Human CD44 is Characteristically Expressed on Human Mesenchymal Stem Cells. Stem Cells. 2016; 35(4):1080-1092. PMC: 5367967. DOI: 10.1002/stem.2549. View

10.

Choi J, Kang M, Nam S, Lee G, Kim H, Ryu J . Bidirectional signaling between TM4SF5 and IGF1R promotes resistance to EGFR kinase inhibitors. Lung Cancer. 2015; 90(1):22-31. DOI: 10.1016/j.lungcan.2015.06.023. View

11.

Liao C, An J, Yi S, Tan Z, Wang H, Li H . FUT8 and Protein Core Fucosylation in Tumours: From Diagnosis to Treatment. J Cancer. 2021; 12(13):4109-4120. PMC: 8176256. DOI: 10.7150/jca.58268. View

12.

Bastian K, Scott E, Elliott D, Munkley J . FUT8 Alpha-(1,6)-Fucosyltransferase in Cancer. Int J Mol Sci. 2021; 22(1). PMC: 7795606. DOI: 10.3390/ijms22010455. View

13.

Jackson D, Bell J, Dickinson R, Timans J, Shields J, Whittle N . Proteoglycan forms of the lymphocyte homing receptor CD44 are alternatively spliced variants containing the v3 exon. J Cell Biol. 1995; 128(4):673-85. PMC: 2199896. DOI: 10.1083/jcb.128.4.673. View

14.

Sarkar A, Chanda A, Regmi S, Karve K, Deng L, Jay G . Recombinant human PRG4 (rhPRG4) suppresses breast cancer cell invasion by inhibiting TGFβ-Hyaluronan-CD44 signalling pathway. PLoS One. 2019; 14(7):e0219697. PMC: 6667139. DOI: 10.1371/journal.pone.0219697. View

15.

Springer A, Dowdy S . GalNAc-siRNA Conjugates: Leading the Way for Delivery of RNAi Therapeutics. Nucleic Acid Ther. 2018; 28(3):109-118. PMC: 5994659. DOI: 10.1089/nat.2018.0736. View

16.

Yamano S, Gi M, Tago Y, Doi K, Okada S, Hirayama Y . Role of deltaNp63(pos)CD44v(pos) cells in the development of N-nitroso-tris-chloroethylurea-induced peripheral-type mouse lung squamous cell carcinomas. Cancer Sci. 2015; 107(2):123-32. PMC: 4768398. DOI: 10.1111/cas.12855. View

17.

Jones M, Tussey L, Athanasou N, Jackson D . Heparan sulfate proteoglycan isoforms of the CD44 hyaluronan receptor induced in human inflammatory macrophages can function as paracrine regulators of fibroblast growth factor action. J Biol Chem. 2000; 275(11):7964-74. DOI: 10.1074/jbc.275.11.7964. View

18.

Shi H, Jiang C, Yao H, Zhang Y, Zhang Q, Hou X . CD44 fucosylation on bone marrow-derived mesenchymal stem cells enhances homing and promotes enteric nervous system remodeling in diabetic mice. Cell Biosci. 2021; 11(1):118. PMC: 8243650. DOI: 10.1186/s13578-021-00632-2. View

19.

Zaiden M, Rutter M, Shpirt L, Ventura Y, Feinshtein V, David A . CD44-Targeted Polymer-Paclitaxel Conjugates to Control the Spread and Growth of Metastatic Tumors. Mol Pharm. 2018; 15(9):3690-3699. DOI: 10.1021/acs.molpharmaceut.8b00269. View

20.

Suzuki-Inoue K . Platelets and cancer-associated thrombosis: focusing on the platelet activation receptor CLEC-2 and podoplanin. Blood. 2019; 134(22):1912-1918. DOI: 10.1182/blood.2019001388. View