Cross talk between hedgehog and epithelial-mesenchymal transition pathways in gastric pit cells and in diffuse-type gastric cancers.
Cross talk between hedgehog and epithelial-mesenchymal transition pathways in gastric pit cells and in diffuse-type gastric cancers.
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DOI：
10.1038/sj.bjc.6604846
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发表时间：
2009-01-27
影响因子：
8.8
通讯作者：
Sasaki, H.
中科院分区：
文献类型：
--
作者：
Ohta, H.;Aoyagi, K.;Fukaya, M.;Danjoh, I.;Ohta, A.;Isohata, N.;Saeki, N.;Taniguchi, H.;Sakamoto, H.;Shimoda, T.;Tani, T.;Yoshida, T.;Sasaki, H.
关键词：
我们先前报道了刺猬（Hh）信号激活的粘液分泌小凹细胞的胃和弥漫型胃癌（GC）。上皮间质转化（EMT）是已知的参与肿瘤恶性。然而，很少有人知道这两个信号是否以及如何在扩散型GC中协同作用。通过基因芯片和逆转录-PCR技术，我们研究了这些Hh和EMT信号分子在窝细胞和弥漫型GC中的表达。还通过在小鼠原代培养物和人GC细胞系上处理Hh-信号抑制剂和Hh和EMT转录关键调节基因的siRNA来研究这两种信号传导如何在这些细胞中协同作用。陷窝细胞和弥漫型GC共表达许多Hh和EMT信号基因。间质相关基因（WNT 5A，CDH 2，PDGFRB，EDNRA，ROBO 1，ROR 2和MEF 2C）被EMT调节因子SIP 1/ZFHX 1B/ZEB 2激活，SIP 1/ZFHX 1B/ZEB 2是Hh信号中主要转录调节因子GLI 1的靶点。此外，我们确定了两个癌症特异性Hh靶点，ELK 1和MSX 2，它们在GC细胞生长中起着重要作用。这些结果表明，胃小凹细胞表现出间充质样基因表达，弥漫型GC通过Hh-EMT途径维持表达。我们提出的广泛的Hh-EMT信号通路具有理解弥漫型GC和开发新药的潜力。
We previously reported hedgehog (Hh) signal activation in the mucus-secreting pit cell of the stomach and in diffuse-type gastric cancer (GC). Epithelial–mesenchymal transition (EMT) is known to be involved in tumour malignancy. However, little is known about whether and how both signallings cooperatively act in diffuse-type GC. By microarray and reverse transcription–PCR, we investigated the expression of those Hh and EMT signalling molecules in pit cells and in diffuse-type GCs. How both signallings act cooperatively in those cells was also investigated by the treatment of an Hh-signal inhibitor and siRNAs of Hh and EMT transcriptional key regulator genes on a mouse primary culture and on human GC cell lines. Pit cells and diffuse-type GCs co-expressed many Hh and EMT signalling genes. Mesenchymal-related genes (WNT5A, CDH2, PDGFRB, EDNRA, ROBO1, ROR2, and MEF2C) were found to be activated by an EMT regulator, SIP1/ZFHX1B/ZEB2, which was a target of a primary transcriptional regulator GLI1 in Hh signal. Furthermore, we identified two cancer-specific Hh targets, ELK1 and MSX2, which have an essential role in GC cell growth. These findings suggest that the gastric pit cell exhibits mesenchymal-like gene expression, and that diffuse-type GC maintains expression through the Hh–EMT pathway. Our proposed extensive Hh–EMT signal pathway has the potential to an understanding of diffuse-type GC and to the development of new drugs.
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影响因子：
11.2
作者：
Nishigaki, M;Aoyagi, K;Sasaki, H
通讯作者：
Sasaki, H
DOI：
10.1111/apm.1965.64.1.31
发表时间：
1965-01-01
期刊：
ACTA PATHOLOGICA ET MICROBIOLOGICA SCANDINAVICA
影响因子：
--
作者：
LAUREN, P
通讯作者：
LAUREN, P
影响因子：
11.2
作者：
Kurayoshi, Manabu;Oue, Naohide;Kikuchi, Akira
通讯作者：
Kikuchi, Akira
DOI：
10.1007/s10120-005-0321-z
发表时间：
2005-01-01
期刊：
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
影响因子：
--
作者：
Lordick, Florian;Siewert, J Rudiger
通讯作者：
Siewert, J Rudiger
影响因子：
8
作者：
Saeki, N.;Kim, D. H.;Sasaki, H.
通讯作者：
Sasaki, H.