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Potential of Tyrosine Kinase Receptor TIE-1 as Novel Therapeutic Target in High-PI3K-Expressing Ovarian Cancer

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
Laboratory of Immunopharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 572-8508, Japan
Department of Obstetrics and Gynecology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki 986-8522, Japan
Author to whom correspondence should be addressed.
Cancers 2020, 12(6), 1705;
Received: 12 May 2020 / Revised: 17 June 2020 / Accepted: 23 June 2020 / Published: 26 June 2020
(This article belongs to the Section Molecular Cancer Biology)
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. View Full-Text
Keywords: TIE-1; PI3K; ovarian cancer; molecular targeted therapy TIE-1; PI3K; ovarian cancer; molecular targeted therapy
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Zhang, X.; Ishibashi, M.; Kitatani, K.; Shigeta, S.; Tokunaga, H.; Toyoshima, M.; Shimada, M.; Yaegashi, N. Potential of Tyrosine Kinase Receptor TIE-1 as Novel Therapeutic Target in High-PI3K-Expressing Ovarian Cancer. Cancers 2020, 12, 1705.

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