A cell-autonomous PD-1/PD-L1 circuit promotes tumorigenicity of thyroid cancer cells by activating a SHP2/Ras/MAPK signalling cascade
Liotti, F.; Kumar, N.; Prevete, N.; Marotta, M.; Sorriento, D.; Ierano, C.; Ronchi, A.; Zito Marino, F.; Moretti, S.; Colella, R.; Puxeddu, E.; Paladino, S.; Kano, Y.; Ohh, M.; Scala, S.; Melillo, R. M.
Show abstract
The programmed cell death-1 (PD-1) and its ligands PD-L1 and PD-L2 are immune checkpoints. Typically, cancer cells express the PD-Ls that bind PD-1 on immune cells, inhibiting their anti-cancer activity. Recently, PD-1 expression has been found in cancer cells. We analysed expression and functions of PD-1 in thyroid cancer (TC). Human TC specimens (47%), but not normal thyroids, displayed PD-1 expression in epithelial cells, which significantly correlated with tumour stage and lymph-node metastasis. PD-1 overexpression/stimulation promoted TC cell proliferation and migration in culture. PD-1 recruited the SHP2 phosphatase, potentiated its phosphatase activity thus enhancing Ras activation by dephosphorylation of inhibitory tyrosine 32 and triggering the MAPK cascade. PD-1 inhibition decreased, while PD-1 overexpression facilitated, TC cell xenograft growth by affecting cell proliferation. PD-1 circuit blockade in TC, besides restoring anti-cancer immunity, could also directly impair TC cell growth by inhibiting the Ras/MAPK pathway.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- LRRK2-phosphorylated Rab10 sequesters Myosin Va with RILPL2 during ciliogenesis blockade 92%
- The ADAM17 sheddase complex regulator iTAP modulates inflammation, epithelial repair, and tumor growth 92%
- ETV2 regulates PARP-1 binding protein to induce ER stress-mediated cell death in tuberin-deficient cells 92%
Similar papers in this journal
Similar papers in this journal
- MAPK-induced miR-29 targets MAFG and suppresses melanoma development 92%
- PRMT1 regulates EGFR and Wnt signaling pathways and is a promising target for combinatorial treatment of breast cancer 91%
- Blocking Gi/o-coupled signaling eradicates cancer stem cells and sensitizes breast tumors to HER2-targeted therapies to inhibit tumor relapse 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.