Department of Surgery and Medical Research, Far Eastern Memorial Hospital, New Taipei 220, Taiwan.
Int J Mol Sci. 2020 Jan 23;21(3):758. doi: 10.3390/ijms21030758.
During mammalian embryonic development, primary cilia transduce and regulate several signaling pathways. Among the various pathways, Sonic hedgehog (SHH) is one of the most significant. SHH signaling remains quiescent in adult mammalian tissues. However, in multiple adult tissues, it becomes active during differentiation, proliferation, and maintenance. Moreover, aberrant activation of SHH signaling occurs in cancers of the skin, brain, liver, gallbladder, pancreas, stomach, colon, breast, lung, prostate, and hematological malignancies. Recent studies have shown that the tumor microenvironment or stroma could affect tumor development and metastasis. One hypothesis has been proposed, claiming that the pancreatic epithelia secretes SHH that is essential in establishing and regulating the pancreatic tumor microenvironment in promoting cancer progression. The SHH signaling pathway is also activated in the cancer stem cells (CSC) of several neoplasms. The self-renewal of CSC is regulated by the SHH/Smoothened receptor (SMO)/Glioma-associated oncogene homolog I (GLI) signaling pathway. Combined use of SHH signaling inhibitors and chemotherapy/radiation therapy/immunotherapy is therefore key in targeting CSCs.
在哺乳动物胚胎发育过程中，初级纤毛转导并调节几种信号通路。在各种信号通路中，Sonic hedgehog（SHH）信号通路是最重要的信号通路之一。在成年哺乳动物组织中，SHH 信号通路处于静止状态。然而，在多种成年组织中，它在分化、增殖和维持过程中变得活跃。此外，SHH 信号通路的异常激活发生在皮肤、脑、肝、胆囊、胰腺、胃、结肠、乳腺、肺、前列腺和血液恶性肿瘤中。最近的研究表明，肿瘤微环境或基质可能会影响肿瘤的发展和转移。有一种假设认为，胰腺上皮细胞分泌的 SHH 对于建立和调节促进癌症进展的胰腺肿瘤微环境是必不可少的。SHH 信号通路也在几种肿瘤的癌症干细胞（CSC）中被激活。CSC 的自我更新受 SHH/Smoothened 受体（SMO）/Glioma-associated oncogene homolog I（GLI）信号通路的调节。因此，联合使用 SHH 信号通路抑制剂和化疗/放疗/免疫疗法是靶向 CSC 的关键。
