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

Nature Communications
Liang ZhaoCharles S Abrams

Abstract

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.

References

Aug 30, 1974·Brain Research·M J BrownsteinJ Axelrod
Mar 5, 1996·Proceedings of the National Academy of Sciences of the United States of America·P StassensG P Vlasuk
Sep 28, 1999·British Journal of Pharmacology·Y DobrydnevaP F Blackmore
Mar 22, 2002·Molecular Biology of the Cell·James G AlbVytas A Bankaitis
Nov 13, 2003·Proceedings of the National Academy of Sciences of the United States of America·Suzanne J BakewellKatherine N Weilbaecher
Mar 23, 2004·Seminars in Thrombosis and Hemostasis·Ewa Sierko, Marek Z Wojtukiewicz
Jun 2, 2004·Nature Cell Biology·Maria Antonietta De Matteis, Anna Godi
Jul 28, 2004·The Journal of Biological Chemistry·Seun-Ah YangCharles S Abrams
Jan 25, 2006·Current Biology : CB·Maria Grazia GiansantiMaurizio Gatti
Oct 13, 2006·Nature·Gilbert Di Paolo, Pietro De Camilli
May 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Shashank JainJerry Ware
Jan 29, 2008·Blood·Kenneth Kaushansky
Sep 6, 2008·Proceedings of the National Academy of Sciences of the United States of America·Yanfeng WangCharles S Abrams
Sep 5, 2009·The American Journal of Pathology·Benoit Ho-Tin-NoéDenisa D Wagner
Jan 25, 2011·Nature Reviews. Cancer·Laurie J Gay, Brunhilde Felding-Habermann
Sep 8, 2012·Circulation Research·Shuchi GuptaBernhard Nieswandt
Jun 13, 2013·Blood·Sang H Min, Charles S Abrams
Apr 20, 2012·World Journal of Experimental Medicine·Yang LiuXiao-Jun Du

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Citations

Jun 17, 2020·Expert Opinion on Drug Delivery·Qirong TongGuangxi Zhai
Mar 3, 2020·Frontiers in Immunology·Stefanie MaurerKorbinian N Kropp
Apr 17, 2020·Platelets·Timothy J Stalker
Jun 11, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Tim G AshlinShamshad Cockcroft

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