Autotaxin-β interaction with the cell surface via syndecan-4 impacts on cancer cell proliferation and metastasis

Raphael Leblanc, Debashish Sahay, Audrey Houssin, Irma Machuca-Gayet, Olivier Peyruchaud

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Autotaxin (ATX) promotes cancer cell metastasis through the production of lysophosphatidic acid (LPA). ATX binds to avβ3 integrins controlling metastasis of breast cancer cells. We screened a series of cancer cell lines derived from diverse human and mouse solid tumors for the capacity of binding to ATX and found only a modest correlation with their level of avβ3 integrin expression. These results strongly suggested the existence of another cell surface ATX-interacting factor. Indeed, ATXa has been shown to bind heparan-sulfate chains because of its unique polybasic insertion sequence, although the biological significance is unknown. We demonstrated here, that among all cell surface heparan-sulfate proteoglycans, syndecan-4 (SDC4) was essential for cancer cell interaction with ATXβ but was restrained by heparan-sulfate chains. In addition, exogenous ATXβ-induced MG63 osteosarcoma cell proliferation required physical interaction of ATXβ with the cell surface via an SDC4-dependent mechanism. In a preclininal mouse model, targeting SDC4 on 4T1 mouse breast cancer cells inhibited early bone metastasis formation. Furthermore, SDC4-prometastatic activity was totally abolished in absence of ATX expression. In conclusion our results determined that ATX and SDC4 are engaged in a reciprocal collaboration for cancer cell metastasis providing the rational for the development of novel anti-metastasis therapies.

Original languageEnglish
Pages (from-to)33170-33185
Number of pages16
Issue number69
StatePublished - 1 Sep 2018
Externally publishedYes


  • Adhesion
  • Autotaxin
  • Heparan sulfate proteoglycans
  • Metastasis
  • Syndecan-4


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