Researchers Decipher Blood Cell Signaling Process that Aids Cancer Spread

Cancer often spreads throughout the body via the bloodstream. However, once cancer cells have been transported to new locations, they have to find a way through the wall around blood vessels to invade new tissues. Researchers have now discovered that when blood platelets, the cells responsible for blood clotting, are activated, they release a molecule called ATP. ATP then binds to a protein called P2Y2 on the blood vessel wall, causing small openings to appear, which cancer cells can use to escape the blood vessel. Blocking ATP release from blood platelets inhibited cancer spread in mouse models of lung cancer and melanoma. Drugs that inhibit ATP release from platelets or block P2Y2 may therefore be able to curb cancer spread.


Platelet-Derived Nucleotides Promote Tumor-Cell Transendothelial Migration and Metastasis via P2Y2 Receptor

“Tumor cells can activate platelets, which in turn facilitate tumor cell survival and dissemination. The exact mechanisms by which platelets promote metastasis have remained unclear. Here, we show that adenine nucleotides released from tumor cell-activated platelets induce opening of the endothelial barrier to allow transendothelial migration of tumor cells and thereby promote cancer cell extravasation. We identified the endothelial P2Y2 receptor, which is activated by ATP, as the primary mediator of this effect. Mice deficient in P2Y2 or lacking ATP secretion from platelets show strongly reduced tumor cell metastasis. These findings demonstrate a mechanism by which platelets promote cancer cell metastasis and suggest the P2Y2 receptor and its endothelial downstream signaling mechanisms as a target for antimetastatic therapies.”


Platelet-Derived Nucleotides Promote Tumor-Cell Transendothelial Migration and Metastasis via P2Y2 Receptor

“Tumor cells can activate platelets, which in turn facilitate tumor cell survival and dissemination. The exact mechanisms by which platelets promote metastasis have remained unclear. Here, we show that adenine nucleotides released from tumor cell-activated platelets induce opening of the endothelial barrier to allow transendothelial migration of tumor cells and thereby promote cancer cell extravasation. We identified the endothelial P2Y2 receptor, which is activated by ATP, as the primary mediator of this effect. Mice deficient in P2Y2 or lacking ATP secretion from platelets show strongly reduced tumor cell metastasis. These findings demonstrate a mechanism by which platelets promote cancer cell metastasis and suggest the P2Y2 receptor and its endothelial downstream signaling mechanisms as a target for antimetastatic therapies.”


Platelet-Derived Nucleotides Promote Tumor-Cell Transendothelial Migration and Metastasis via P2Y2 Receptor

“Tumor cells can activate platelets, which in turn facilitate tumor cell survival and dissemination. The exact mechanisms by which platelets promote metastasis have remained unclear. Here, we show that adenine nucleotides released from tumor cell-activated platelets induce opening of the endothelial barrier to allow transendothelial migration of tumor cells and thereby promote cancer cell extravasation. We identified the endothelial P2Y2 receptor, which is activated by ATP, as the primary mediator of this effect. Mice deficient in P2Y2 or lacking ATP secretion from platelets show strongly reduced tumor cell metastasis. These findings demonstrate a mechanism by which platelets promote cancer cell metastasis and suggest the P2Y2 receptor and its endothelial downstream signaling mechanisms as a target for antimetastatic therapies.”


RAF Inhibitors Activate the MAPK Pathway by Relieving Inhibitory Autophosphorylation

“ATP competitive inhibitors of the BRAFV600E oncogene paradoxically activate downstream signaling in cells bearing wild-type BRAF (BRAFWT). In this study, we investigate the biochemical mechanism of wild-type RAF (RAFWT) activation by multiple catalytic inhibitors using kinetic analysis of purified BRAFV600E and RAFWT enzymes. We show that activation of RAFWT is ATP dependent and directly linked to RAF kinase activity…”


Chemotherapy Found To Work In An Unexpected Way

It’s generally thought that anticancer chemotherapies work like antibiotics do, by directly killing off what’s harmful. But new research published online in the Cell Press journal Immunity


Chemotherapy Found To Work In An Unexpected Way

It’s generally thought that anticancer chemotherapies work like antibiotics do, by directly killing off what’s harmful. But new research published online in the Cell Press journal Immunity


Chemotherapy Found To Work In An Unexpected Way

It’s generally thought that anticancer chemotherapies work like antibiotics do, by directly killing off what’s harmful. But new research published online in the Cell Press journal Immunity