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PI3K/Akt/YAP信号通路促进DLD-1结肠癌细胞的迁移和侵袭。

PI3K/Akt/YAP signaling promotes migration and invasion of DLD-1 colorectal cancer cells.

作者信息

Takeda Tomoya, Yamamoto Yuuta, Tsubaki Masanobu, Matsuda Takuya, Kimura Akihiro, Shimo Natsumi, Nishida Shozo

机构信息

Division of Pharmacotherapy, Kindai University School of Pharmacy, Higashi-Osaka, Osaka 577-8502, Japan.

出版信息

Oncol Lett. 2022 Apr;23(4):106. doi: 10.3892/ol.2022.13226. Epub 2022 Feb 3.

Abstract

Colorectal cancer (CRC) is one of the most prevalent malignant diseases and metastasis is the leading cause of poor prognosis in patients with CRC. Further knowledge of the molecular mechanism underlying metastasis in CRC and the identification of new therapeutic targets are needed. Yes-associated protein (YAP) is a transcriptional regulator that is important in tumorigenesis and tumor cell proliferation. The present study investigated whether YAP was crucial for CRC migration and invasion. The protein expression levels were detected via western blotting, and migration and invasion were analyzed by Transwell migration and invasion assays. Subsequently, YAP expression was silenced using small interfering RNA. The mRNA expression levels were detected via reverse transcription-quantitative PCR and cell viability was assessed via Trypan blue exclusion assay. The results revealed that YAP protein levels were associated with migration and invasion of CRC cells. Notably, YAP small interfering RNA inhibited the migration and invasion of DLD-1 cells. In addition, the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway inhibitor LY294002 suppressed the migration and invasion of DLD-1 cells by decreasing the expression of YAP. Notably, the present study demonstrated that verteporfin mediated the suppression of migration and invasion of DLD-1 cells due to the decreased expression of YAP. Therefore, targeting YAP may be valuable for developing therapeutic strategies against CRC, and verteporfin may be an effective therapy to suppress the migration and invasion of CRC.

摘要

结直肠癌(CRC)是最常见的恶性疾病之一,转移是CRC患者预后不良的主要原因。需要进一步了解CRC转移的分子机制并确定新的治疗靶点。Yes相关蛋白(YAP)是一种转录调节因子,在肿瘤发生和肿瘤细胞增殖中起重要作用。本研究调查了YAP对CRC迁移和侵袭是否至关重要。通过蛋白质印迹法检测蛋白质表达水平,并通过Transwell迁移和侵袭试验分析迁移和侵袭情况。随后,使用小干扰RNA使YAP表达沉默。通过逆转录定量PCR检测mRNA表达水平,并通过台盼蓝排斥试验评估细胞活力。结果显示,YAP蛋白水平与CRC细胞的迁移和侵袭相关。值得注意的是,YAP小干扰RNA抑制了DLD-1细胞的迁移和侵袭。此外,磷酸肌醇3-激酶(PI3K)/Akt信号通路抑制剂LY294002通过降低YAP的表达抑制了DLD-1细胞的迁移和侵袭。值得注意的是,本研究表明维替泊芬由于YAP表达降低介导了对DLD-1细胞迁移和侵袭的抑制作用。因此,靶向YAP可能对开发针对CRC的治疗策略有价值,并且维替泊芬可能是抑制CRC迁移和侵袭的有效疗法。

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