Zhang Xuewei, Ishibashi Masumi, Kitatani Kazuyuki, Shigeta Shogo, Tokunaga Hideki, Toyoshima Masafumi, Shimada Muneaki, Yaegashi Nobuo
Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Tohoku University, Sendai 980-8577, Japan.
Cancer Science Institute of Singapore, National University of Singapore, Singapore 119077, Singapore.
Cancers (Basel). 2020 Jun 26;12(6):1705. doi: 10.3390/cancers12061705.
Tyrosine kinase receptor TIE-1 plays a critical role in angiogenesis and blood-vessel stability. In recent years, increased TIE-1 expression has been observed in many types of cancers; however, the biological significance and underlying mechanisms remain unknown. Thus, in the present study, we investigated the tumor biological functions of TIE-1 in ovarian cancer. The treatment of SKOV3 ovarian-cancer cells with siRNA against TIE-1 decreased the expression of key molecules in the PI3K/Akt signaling pathway, such as p110α and phospho-Akt, suggesting that TIE-1 is related to the PI3K/Akt pathway. Furthermore, the knockdown of TIE-1 significantly decreased cell proliferation in high-PI3K-expressing cell lines (SKOV3, CAOV3) but not low-PI3K-expressing cell lines (TOV112D, A2780). These results suggested that inhibition of TIE-1 decreases cell growth in high-PI3K-expressing cells. Moreover, in low-PI3K-expressing TOV112D ovarian-cancer cells, TIE-1 overexpression induced PI3K upregulation and promoted a PI3K-mediated cell proliferative phenotype. Mechanistically, TIE-1 participates in cell growth and proliferation by regulating the PI3K/Akt signaling pathway. Taken together, our findings strongly implicate TIE-1 as a novel therapeutic target in high-PI3K-expressing ovarian-cancer cells.
酪氨酸激酶受体TIE-1在血管生成和血管稳定性中起关键作用。近年来，在多种癌症中均观察到TIE-1表达增加；然而，其生物学意义和潜在机制仍不清楚。因此，在本研究中，我们调查了TIE-1在卵巢癌中的肿瘤生物学功能。用针对TIE-1的小干扰RNA（siRNA）处理SKOV3卵巢癌细胞，可降低PI3K/Akt信号通路中关键分子如p110α和磷酸化Akt的表达，提示TIE-1与PI3K/Akt通路相关。此外，敲低TIE-1可显著降低高表达PI3K的细胞系（SKOV3、CAOV3）中的细胞增殖，但对低表达PI3K的细胞系（TOV112D、A2780）无此作用。这些结果表明，抑制TIE-1可降低高表达PI3K细胞中的细胞生长。此外，在低表达PI3K的TOV112D卵巢癌细胞中，TIE-1过表达可诱导PI3K上调并促进PI3K介导的细胞增殖表型。从机制上讲，TIE-1通过调节PI3K/Akt信号通路参与细胞生长和增殖。综上所述，我们的研究结果强烈表明TIE-1是高表达PI3K的卵巢癌细胞中的一个新的治疗靶点。
