Phosphatidylinositol transfer protein-α in platelets is inconsequential for thrombosis yet is utilized for tumor metastasis

Nat Commun. 2017 Oct 31;8(1):1216. doi: 10.1038/s41467-017-01181-4.


Platelets are increasingly recognized for their contributions to tumor metastasis. Here, we show that the phosphoinositide signaling modulated by phosphatidylinositol transfer protein type α (PITPα), a protein which shuttles phosphatidylinositol between organelles, is essential for platelet-mediated tumor metastasis. PITPα-deficient platelets have reduced intracellular pools of phosphoinositides and an 80% reduction in IP3 generation upon platelet activation. Unexpectedly, mice lacking platelet PITPα form thrombi normally at sites of intravascular injuries. However, following intravenous injection of tumor cells, mice lacking PITPα develop fewer lung metastases due to a reduction of fibrin formation surrounding the tumor cells, rendering the metastases susceptible to mucosal immunity. These findings demonstrate that platelet PITPα-mediated phosphoinositide signaling is inconsequential for in vivo hemostasis, yet is critical for in vivo dissemination. Moreover, this demonstrates that signaling pathways within platelets may be segregated into pathways that are essential for thrombosis formation and pathways that are important for non-hemostatic functions.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anticoagulants / pharmacology
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • Blood Platelets / pathology
  • Fibrin / metabolism
  • Gene Deletion
  • Hemostasis / drug effects
  • Hyperplasia
  • Immunity, Mucosal / drug effects
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Integrases / metabolism
  • Lung Neoplasms / secondary*
  • Lymphoid Tissue / pathology
  • Male
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Phospholipid Transfer Proteins / metabolism*
  • Platelet Aggregation / drug effects
  • Signal Transduction / drug effects
  • Thrombin / metabolism
  • Thrombosis / metabolism*
  • Thrombosis / pathology


  • Anticoagulants
  • Phospholipid Transfer Proteins
  • Inositol 1,4,5-Trisphosphate
  • Fibrin
  • Cre recombinase
  • Integrases
  • Thrombin