In addition, RES has been reported to inhibit tumorigenesis in several animal

Increased cell death was also observed in AML via knock down of SYK, Further studies are needed to discriminate between overexpression versus activation of SYK in SCLC. Our findings unveil an unsuspected link between SCLC and the biology 17-AAG 分子量 of B cell leukemias lymphomas that is worth exploring. The role of SYK in B cell recep tor initiated tonic signaling both in normal B cells and lymphomas is well established, Tonic signaling promotes proliferation and survival of B cells. Mice lacking SYK exhibit profound B cell development deficits, and die embryonically from severe hemorrhages, also pointing to indispensable SYK signaling in cell types other than B cells, Targeted SYK therapy has been advocated in various types of B cell lymphomas, and specific inhibitors for its kinase activity are already approved such as R406, fostamatinib, opening avenues for testing targeted treatment in SCLC.<br><br> SYK signaling in NE may be asso ciated with oxygen sensing, but SYK associated receptor in NE or SCLC cells remain to be defined. There are several reports of tumor suppressor functions for SYK in several solid tumor types, including breast can cer, gastric cancer, and melanoma, Additional data are needed 17-DMAG ic50 to reconcile these seemingly conflicting roles of SYK as oncogene or tumor suppressor. In this regard, it is worth noting that in B cells effects of SYK on survival and proliferation are modulated by associated SRC family kinase members, Differential interactions of SYK with such kinases in a tumor specific manner are a possible explanation for the dual role of SYK as a tumor suppressor in some cancers, and an oncogene in hematologic malignancies and SCLC.<br><br> Therefore, an immediate priority is to determine the type of receptor SYK is associated with in SCLC, and its possible regulation by SRC family kinases such as FYN, In agreement A66 価格 with our results, in the Cancer Cell Line Encyclopedia, 35 out of 49 SCLC cell lines tested overexpress SYK, In another recent large dataset 33 of 53 SCLC cell lines overexpress SYK, We confined our experimenta tion to SCLC cultured cell lines and knock down of SYK expression. While our data are encouraging, future studies should address applicability to spontaneous or human xenotransplant mouse models of SCLC, Furthermore, it remains to be seen whether inhibition of SYK kinase activity, in addition to expression, elicits a death response in SCLC.<br><br> It is worth noting that to date no SYK mutations have been reported in any tumor type. SYK gene fusions or translocations have been reported in hematologic malig nancies, in which a driver function for overexpressed SYK has also been postulated, On the other hand, SYK negative tumors have hypermethylation and loss of function of the SYK gene, Thus, the biology of SYK positive SCLC tumors may be potentially distinct from SYK negative SCLC tumors, with differences due to stages of progression, or divergence of transforming mechanisms.