YY1 targets tubulin polymerisation-promoting protein to inhibit migration, invasion and angiogenesis in pancreatic cancer via p38/MAPK and PI3K/AKT pathways
YY1 targets tubulin polymerisation-promoting protein to inhibit migration, invasion and angiogenesis in pancreatic cancer via p38/MAPK and PI3K/AKT pathways
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YY1 靶向微管蛋白聚合促进蛋白，通过 p38/MAPK 和 PI3K/AKT 途径抑制胰腺癌的迁移、侵袭和血管生成
DOI：
10.1038/s41416-019-0604-5
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发表时间：
2019-11-26
影响因子：
8.8
通讯作者：
Jiang, Kui-Rong
中科院分区：
文献类型：
--
作者：
Chen, Qun;Yang, Chuang;Jiang, Kui-Rong
背景胰腺癌（pancreatic cancer，PDAC）是一种高度侵袭性、预后差的恶性肿瘤.最近的研究发现，转录因子Yin Yang 1（YY 1）在胰腺癌的发展中起抑制作用。据报道，微管蛋白聚合促进蛋白（TPPP）在各种肿瘤中起着不可或缺的作用，但其在胰腺癌中的表达和作用尚未阐明。MethodsIn这项研究中，我们进行ChIP测序，发现YY 1直接结合到TPPP的启动子区。采用免疫印迹法和免疫组化法检测胰腺癌组织中TPPP的表达。结果免疫组化显示TPPP在胰腺癌组织中呈低水平表达，且与血管侵袭有关。体内实验结果表明，TPPP可促进胰腺癌的迁移和侵袭。进一步的实验表明，YY 1可通过p38/MAPK和PI 3 K/AKT途径下调TPPP的表达，从而抑制胰腺癌细胞的迁移、侵袭和血管生成。
BackgroundPancreatic cancer (PDAC) is a highly invasive cancer with poor prognosis. Recent research has found that the transcription factor Yin Yang 1 (YY1) plays an inhibitory role in the development of pancreatic cancer. It has been reported that tubulin polymerisation-promoting protein (TPPP) plays an indispensable role in a variety of tumours, but its expression and role in pancreatic cancer have not yet been elucidated.MethodsIn this study, we performed ChIP-sequencing and found that YY1 directly binds to the promoter region of TPPP. The expression of TPPP in pancreatic cancer was detected by western blotting and immunohistochemistry. Four-week-old male BALB/c-nude mice were used to assess the effect of TPPP on pancreatic cancer.ResultsImmunohistochemistry revealed that TPPP was expressed at low levels in pancreatic cancer tissues, and was associated with blood vessel invasion. The results from vivo experiments have showed that TPPP could enhance the migration and invasion of pancreatic cancer. Further experiments showed that YY1 could inhibit the migration, invasion and angiogenesis of pancreatic cancer cells by downregulating TPPP via p38/MAPK and PI3K/AKT pathways.ConclusionOur study demonstrates that TPPP may act as a promoter and may serve as a novel target for the treatment of pancreatic cancer.