分子腫瘤學(xué)5 細(xì)胞信號轉(zhuǎn)導(dǎo)與腫瘤-預(yù)覽頁
【正文】 多種人類血液疾病包括白血病和淋巴瘤 中有特定的 JAK、 STAT活化 STAT3組成性活化可能在具有激活的生長 因子受體信號途徑的腫瘤發(fā)生發(fā)展中起關(guān) 鍵作用 JAK proteins,are stringently maintained in inactive plexes . Cytokinemediated receptor activation and subsequent JAK activation trigger a cascade of signaling events, which control survival, proliferation and differen tiation of different cell types. During the past several years, several JAK mutations have been identified that encode constitutively active or hyperactive JAK proteins, which have crucial roles in hematopoietic malignancies, especially myeloproliferative neoplasms. When expressed in cells and bound to membrane cytokine receptors, mutant JAK proteins are no longer maintained in an inactive state, and they persistently activate STAT proteins . This activity promotes oncogenic transformation and uncontrolled blood cell production. The role of JAK–STAT mutations in cancer has only recently begun to be explored, and it is possible that mutations in ponents of this pathway are present in a wide variety of cancers. Mutations in JAKs and disease association JAKs Substitution Disease association JAK2 (human) V617F MPDs K539L (and the region F537–E543) PV T875N Acute megakaryoblastic myeloid leukemia Deletion of IREED Acute lymphoblastic leukemia (position 682–686) JAK3 (human) A572V Acute megakaryoblastic myeloid leukemia V722I Acute megakaryoblastic myeloid leukemia P132T Acute megakaryoblastic myeloid leukemia JAK1 (human) G871E Uterine leiomyosaras [45] 可能機(jī)制： STAT活化與腫瘤細(xì)胞凋亡異常： STAT3 / STAT5可通過抑制凋亡來介導(dǎo)細(xì)胞惡性演進(jìn)； STAT3/BclxL信號通路在凋亡中發(fā)揮重要作用 STAT活化與腫瘤細(xì)胞周期異常： CyclinD1與 CDK4和 CDK6結(jié)合有助于 G1/S期進(jìn)程，在 CyclinD1調(diào)控區(qū)的 481位有 STAT5的結(jié)合位點，提示 STAT5 通過介導(dǎo) CyclinD1表達(dá)刺激細(xì)胞增殖導(dǎo)致癌變。 在黑色素瘤細(xì)胞中， STAT3可活化金屬蛋白酶 2（ MMP2），降解細(xì)胞外基質(zhì)
教學(xué)課件相關(guān)推薦
鄂ICP備17016276號-1