Hedgehog signaling pathway regulates ovarian cancer invasion and migration via adhesion molecule CD24.
Hedgehog signaling pathway regulates ovarian cancer invasion and migration via adhesion molecule CD24.
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Hedgehog信号通路通过粘附分子CD24调控卵巢癌侵袭和迁移
DOI：
10.7150/jca.17712
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发表时间：
2017
影响因子：
3.9
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Zeng C;Chen T;Zhang Y;Chen Q
Hedgehog（Hh）信号在癌症中起着重要作用;然而，其在卵巢癌迁移和侵袭中的机制仍不清楚。在本研究中，我们的目的是澄清Hh信号通路的影响，卵巢癌的迁移和侵袭，通过调节CD 24的表达，在体外和体内。本研究招募了卵巢癌患者（n = 97）。CD 24表达与患者年龄、组织学类型、淋巴结转移呈负相关（P>0.05），但与临床分期、病理分级呈正相关（p<0.05）。体外实验结果表明，Hh信号传导的抑制剂（Sonic Hedgehog，Shh）和抑制剂（GANT 61）分别显著增强和降低CD 24表达，在基因和蛋白质水平上Shh的加入显著增强了SKOV 3细胞的体外迁移和侵袭能力（p<0.05（p<0.05）使用siRNA下调CD 24抑制Shh的促肿瘤作用，并且体内结果证实GANT 61显著抑制CD 24表达并减少肿瘤生长（p<0.01）。总之，Hh信号可以调节CD 24的表达，CD 24的下调可能在抑制卵巢癌进展中发挥重要作用。
Hedgehog (Hh) signalling plays an important role in cancer; however, its mechanism in ovarian cancer migration and invasion remains unclear. In the present study, we aimed to clarify the effect of the Hh signalling pathway on ovarian cancer migration and invasion through the regulation of CD24 expression, both in vitro and in vivo. Patients with ovarian cancer (n = 97) were recruited for this study. Evaluation of the explored the role parameters of patients indicated that CD24 expression was negatively associated with age, histological type and lymph node metastasis (p>0.05), but was positively associated with the clinical stage and pathological grading (p<0.05).The in vitro results indicated that the activator (sonic hedgehog, Shh) and inhibitor (GANT61) of Hh signalling significantly enhanced and reduced CD24 expression, respectively, at both the gene and protein levels (p<0.05).The addition of Shh significantly enhanced cellular migration and invasion of SKOV3 cells in vitro (p<0.05) Down regulation of CD24 using siRNA inhibited the tumour-promoting effects of Shh, and the in vivo results confirmed that GANT61 significantly inhibited CD24 expression and reduced tumour growth (p<0.01). In conclusion, the expression of CD24 can be regulated by Hh signalling, and downregulation of CD24 could play an important role in inhibiting ovarian cancer progression.