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

Abstract

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.

FLI1 regulates radiotherapy resistance in nasopharyngeal carcinoma through TIE1-mediated PI3K/AKT signaling pathway

“…4 B, C). Since FLI1 regulates the expression of its target genes by binding to their promoter regions, we explored whether it directly modulated the expression of TIE1, which has been reported to promote XPC-dependent nucleotide excision repair (NER) and chemotherapy resistance [ 38 ]. hTFtarget ChIP-seq database also indicated that FLI1 might transcriptionally regulate TIE1 by binding to its promoter region (Additional file 3: hTFtarget ChIP-seq data).…”

“…Accumulating evidence suggests that PI3K/AKT signaling pathway is associated with radioresistance of cancers [ 40 – 42 ]. TIE1 has been reported to be related to the PI3K/AKT signaling pathway in ovarian cancer [ 38 ]. KEGG pathway analysis indicated that FLI1 regulated PI3K/AKT signaling pathway (Fig.…”

“…In non-small cell lung carcinoma cells, it contributes to cisplatin resistance through promoting cell stemness [ 63 ]. Additionally, it regulates PI3K/AKT signaling, which is critical in cancer radiotherapy and chemotherapy resistance [ 38 , 42 ]. Our results from ChIP and luciferase reporter assays showed that FLI1 activated the transcription of TIE1 by binding to its promoter region from -1735 to -1507.…”

“…In ovarian cancer, TIE1 promotes XPC-dependent nucleotide excision repair (NER) to render platinum reagents resistance [ 37 ]. Moreover, TIE1 plays a critical role in ovarian cancer cell proliferation and growth by modulating the PI3K/AKT signaling pathway [ 38 ].…”