The PI3K/Akt pathway upregulates Id1 and integrin α4 to enhance recruitment of human ovarian cancer endothelial progenitor cells.
BACKGROUND
Endothelial progenitor cells (EPCs) contribute to tumor angiogenesis and growth. We aimed to determine whether inhibitors of differentiation 1 (Id1) were expressed in circulating EPCs of patients with ovarian cancer, whether Id1 could mediate EPCs mobilization and recruitment, and, if so, what underlying signaling pathway it used.


METHODS
Circulating EPCs cultures were from 25 patients with ovarian cancer and 20 healthy control subjects. Id1 and integrin α4 expression were analyzed by real-time reverse transcription-polymerase chain reaction and western blot. EPCs proliferation, migration, and adhesion were detected by MTT, transwell chamber, and EPCs-matrigel adhesion assays. Double-stranded DNA containing the interference sequences were synthesized according to the structure of a pGCSIL-GFP viral vector and then inserted into a linearized vector. Positive clones were identified as lentiviral vectors that expressed human Id1 short hairpin RNA (shRNA).


RESULTS
Id1 and integrin α4 expression were increased in EPCs freshly isolated from ovarian cancer patients compared to those obtained from healthy subjects. siRNA-mediated Id1 downregulation substantially reduced EPCs function and integrin α4 expression. Importantly, Inhibition of PI3K/Akt inhibited Id1 and integrin α4 expression, resulting in the decreasing biological function of EPCs.


CONCLUSIONS
Id1 induced EPCs mobilization and recruitment is mediated chiefly by the PI3K/Akt signaling pathway and is associated with activation of integrin α4.
Su
Yajuan
Y
Department of Clinical Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, China. nfyyzl@163.com
Zheng
Lei
L
Wang
Qian
Q
Bao
Jie
J
Cai
Zhen
Z
Liu
Ailan
A
D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D016022:Case-Control Studies; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D039441:Integrin alpha4 / Q000378:metabolism*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D055815:Young Adult
C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D039441:Integrin alpha4; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
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