TIE1

Case Study 1: Tomoka Misawa, 2021

Ovarian cancer is the most lethal gynecologic malignancy due to the tumor's acquisition of chemoresistance to platinum-based chemotherapy. To solve this problem, we conducted RNAi-based large-scale screening and determined that tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE-1) is a key molecule involved in the platinum resistance of ovarian cancer cells. Recently, a variety of studies have investigated that small extracellular vesicles (sEVs) contribute to the communication between cancer cells, including the development of chemoresistance in ovarian cancer.

TIE-1-overexpressed TOV112D cells, termed TOV112DTIE-1 cells, were established, and sEVs were isolated from TOV112DTIE-1 cells supernatants by ultracentrifugation. The researchers assessed cisplatin sensitivity in recipient cells with TOV112DTIE-1-derived sEVs by cell-Titer Glo kit. They also asked whether sEV-derived TIE-1 suppressed the DNA damage response in recipient cells and evaluated the DNA damage response by counting cells positive for DNA damage foci. TIE-1 was contained within sEVTIE-1 derived from the cellular supernatant of TOV112DTIE-1. They showed that sEV-derived TIE-1 decreased chemosensitivity to cisplatin by suppressing the DNA damage response in recipient cells.

Fig1. Immunoblotting for TIE-1, V5 and β-actin in whole cell lysates.

Fig2. Immunoblotting of TIE-1, V5, CD81 and CD9 (exosome marker) in sEVTIE-1.

Case Study 2: Julie Garcia, 2012

Endothelial-mesenchymal transition (EndMT) has a significant role in embryonic heart formation and in various pathologies. However, the molecular mechanisms that regulate EndMT induction remain to be elucidated. The researchers show that suppression of receptor tyrosine kinase Tie1 but not Tie2 induces human endothelial cells to undergo EndMT and that Slug deficiency reverts this process. They find that Erk1/2, Erk5 and Akt cascades control Slug promoter activity induced by Tie1 deficiency. Interestingly, EndMT is present in human pancreatic tumour. They propose that EndMT associated with Tie1 downregulation participates in the pathological development of stroma observed in tumours.

Fig3. Tie1 (left panel) or Tie2 (right panel) siRNA suppresses mRNA and protein expression.

Fig4. Tie1 silencing increases Slug expression. HMVECs were transfected with Tie1 or Ctrl siRNA.

Fig1. Tie-1 in quiescent and angiogenic blood vessels. (Ping Yang, 2015)

Fig2. Proposed model for Tie1-T794 phosphorylation by Rac1/PAK1 and modulation of Rac1 signaling. (Jessica L Reinardy, 2015)

TIE1 involved in several pathways and played different roles in them. We selected most pathways TIE1 participated on our site, such as , which may be useful for your reference. Also, other proteins which involved in the same pathway with TIE1 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

TIE1 has several biochemical functions, for example, ATP binding, protein binding, transmembrane receptor protein tyrosine kinase activity. Some of the functions are cooperated with other proteins, some of the functions could acted by TIE1 itself. We selected most functions TIE1 had, and list some proteins which have the same functions with TIE1. You can find most of the proteins on our site.

TIE1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with TIE1 here. Most of them are supplied by our site. Hope this information will be useful for your research of TIE1.

KRT40; RBPMS; PSG5; MDFI; PTPRC; PTPRG; Dlg4; PTPRJ; HSP90AB1; CDC37