TY - JOUR
T1 - Potential of tyrosine kinase receptor TIE-1 as novel therapeutic target in high-PI3K-expressing ovarian cancer
AU - Zhang, Xuewei
AU - Ishibashi, Masumi
AU - Kitatani, Kazuyuki
AU - Shigeta, Shogo
AU - Tokunaga, Hideki
AU - Toyoshima, Masafumi
AU - Shimada, Muneaki
AU - Yaegashi, Nobuo
N1 - Funding Information:
Funding: This study was financially supported by JSPS KAKENHI grants (18H06172 and 19K21280 to M. Ishibashi).
Funding Information:
This study was financially supported by JSPS KAKENHI grants (18H06172 and 19K21280 to M. Ishibashi). Acknowledgments: We express our gratitude to the laboratory members of the Biomedical Research Unit of Tohoku University Hospital and Department of Obstetrics and Gynecology (Tohoku University, Sendai, Japan) for the critical discussion. We thank the staff at Enago (https://www.enago.jp/).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/6
Y1 - 2020/6
N2 - 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.
AB - 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.
KW - Molecular targeted therapy
KW - Ovarian cancer
KW - PI3K
KW - TIE-1
UR - http://www.scopus.com/inward/record.url?scp=85090720902&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85090720902&partnerID=8YFLogxK
U2 - 10.3390/cancers12061705
DO - 10.3390/cancers12061705
M3 - Article
AN - SCOPUS:85090720902
SN - 2072-6694
VL - 12
SP - 1
EP - 14
JO - Cancers
JF - Cancers
IS - 6
M1 - 1705
ER -
