Integrin β1 regulates proliferation, apoptosis, and migration of trophoblasts through activation of phosphoinositide 3 kinase/protein kinase B signaling

Abstract

Aims Abnormal trophoblast invasion is one of the onsets of preeclampsia (PE). Studies found that integrin β1 (ITGB1) is closely related to PE, but the role of ITGB1 in the progression of trophoblast remained unclear. Therefore, we studied the functional role of ITGB1 in PE and its effects on trophoblast. Methods ITGB1 expression in placenta tissues was determined by quantitative real‐time polymerase chain reaction (qRT‐PCR). The effects of transfection on HTR‐8/SVneo cells were analyzed by qRT‐PCR and western blotting. After cell transfection, colony formation assay, flow cytometry, wound healing assay, and transwell assay were performed to detect cell proliferation, apoptosis, migration, and invasion. Western blotting assay was used for determining phosphoinositide 3 kinase (PI3K) and protein kinase B (Akt) signaling pathway. After inhibiting PI3K/Akt pathway, apoptosis‐regulated proteins were detected by western blotting, and the effects of inhibitor on the migration and invasion changes were examined. Results ITGB1 was downregulated in placenta tissues from PE patients, as compared with normal. ITGB1 overexpression in HTR‐8/SVneo cells enhanced cell proliferation, migration, and invasion, reduced cell apoptosis, and improved phosphorylation of PI3K and Akt. However, ITGB1 depletion resulted in an opposite effect to its overexpression. Inhibition of PI3K/Akt pathway completely blocked the effect of ITGB1 overexpression on cells, because we observed that apoptosis‐regulated proteins were highly upregulated, and that cell migration and invasion were reduced. Conclusion ITGB1 regulated HTR‐8/SVneo cell progression by activation of the PI3K/Akt pathway.

KLF14 targets ITGB1 to inhibit the progression of cervical cancer via the PI3K/AKT signalling pathway

“…ITGB1 is closely correlated with the PI3K/AKT signalling pathway, and many studies have confirmed the relationship between ITGB1 and the PI3K/AKT signalling pathway [ 19 , 32 ]. We considered whether the effect of KLF14 targeting ITGB1 on the progression of cervical cancer was related to the PI3K/AKT signalling pathway.…”

“…With increased research on the integrin signalling pathway and related molecules [ 17 ], integrins have become a hot target in antitumour therapy. Integrin β1 (ITGB1), a member of the integrin (ITG) family, regulates tumour invasion, migration, and apoptosis [ 18 , 19 ]. On this basis, we considered whether KLF14 might be associated with ITGB1, thereby affecting the development of cervical cancer.…”

Determination of WWOX Function in Modulating Cellular Pathways Activated by AP-2α and AP-2γ Transcription Factors in Bladder Cancer

“…The last signaling was transduced by integrins; collectively, they were either decreased or not regulated by WWOX or AP-2α, contrary to AP-2γ which either increased or did not regulate the genes from this group. Increased ITGB1 results in potentiated proliferation, migration, invasion or decreased apoptosis [80], similar to elevated ITGA1 which leads to proliferation or invasion [81]. The remaining integrins of interest, during their overexpression, are responsible for inhibition of both apoptosis and response to therapy (ITGA2) [82], increase in proliferation (ITGA3) [83] or invasion and metastasis intensification (ITGA6) [84].…”

Overexpression of integrin β2 improves migration and engraftment of adipose-derived stem cells and augments angiogenesis in myocardial infarction

“…Apoptosis occurs upon cell detachment from ECM. Integrins are the vital cell-surface receptor for cell-ECM interaction, and they suppress cell apoptosis and resolve the poor survival of implanted cells (22,23). Intercellular cell adhesion molecule-1 (ICAM-1), the ligand for integrin β 2 (ITGB2), is upregulated by muscular ischemia in endothelial cells (24).…”