Wnt5A modulates integrin expression in a receptor-dependent manner in ovarian cancer cells

Abstract

Wnt5A signals through various receptors that confer versatile biological functions. Here, we used Wnt5A overexpressing human ovarian SKOV-3 and OVCAR-3 stable clones for assessing integrin expression, cell proliferation, migration, invasion, and the ability of multicellular aggregates (MCAs) formation. We found here, that Wnt5A regulates differently the expression of its receptors in the stable Wnt5A overexpressing clones. The expression levels of Frizzled (FZD)-2 and -5, were increased in different clones. However ROR-1, -2 expression levels were differently regulated in clones. Wnt5A overexpressing clones showed increased cell proliferation, migration, and clonogenicity. Moreover, Wnt5A overexpressing SKOV-3 clone showed increased MCAs formation ability. Cell invasion had been increased in OVCAR-3-derived clones, while this was decreased in SKOV-3-derived clone. Importantly, αv integrin expression levels were increased in all assessed clones, accompanied by increased cell attachment to fibronectin and focal adhesion kinase activity. Moreover, the treatment of clones with Box5 as a Wnt5A/FZD5 antagonist abrogates ITGAV increase, cell proliferation, migration, and their attachment to fibronectin. Accordingly, we observed significantly higher expression levels of ITGAV and ITGB3 in human high-grade serous ovarian cancer specimens and ITGAV correlated positively with Wnt5A in metastatic serous type ovarian cancer. In summary, we hypothesize here, that Wnt5A/FZD-5 signaling modulate αv integrin expression levels that could be associated with ovarian cancer cell proliferation, migration, and fibronectin attachment.

Expression Profile Analysis to Identify Circular RNA Expression Signatures in the Prolificacy Trait of Yunshang Black Goat Pituitary in the Estrus Cycle

“…However, the function of circRNA–miRNA in the reproductive process needs further validation. In our constructed ceRNA network, chi_circ_0014542 was shown to be a sponge for chi-miR-23b-5p, which targets 20 genes, including the reproductive-associated genes WNT5A and FGFR1 ( Yuan et al, 2019 ; Azimian-Zavareh et al, 2021 ). During the luteal phase, chi_circ_0031209-chi-miR-874-3p and chi_circ_0019448-chi-miR-487a-5p were identified, and they targeted 19 genes and 6 genes, respectively.…”

Wnt5A and TGFβ1 Converges through YAP1 Activity and Integrin Alpha v Up-Regulation Promoting Epithelial to Mesenchymal Transition in Ovarian Cancer Cells and Mesothelial Cell Activation

“…Wnt5A siRNAs (ON-TARGET plus SMART pool human Wnt5A, Cat. 1349-4176 siRNA; Fisher Scientific AG, Wohlen, Switzerland) and non-target siRNAs (ON-TARGET plus SMART pool human NonTarget siRNA, Cat# 1153–7240, Fisher Scientific) were used as specific and negative (scramble) control, respectively as previously described [ 8 , 23 ]. Cell transfection and qRT-PCR were performed and quantified as previously described [ 8 , 23 ].…”

“…Integrin αvβ6 releases TGF-β1 from the LLC, which binds to its receptor, thus activating the pathway [ 22 ]. Recently we reported that Wnt5A induced integrin αv expression in ovarian cancer cells and showed a positive relationship between Wnt5A, αv, and β6 expression in the metastatic human serous ovarian cancer specimens [ 23 ].…”

“…Additionally, inhibition of integrin αv abrogates Wnt5A-induced cell migration [ 23 ]. Our previous report was consistent with the emerging data suggesting that αvβ6 integrin regulates ovarian cancer invasion and metastasis [ 21 , 24 ].…”

Stationed or Relocating: The Seesawing EMT/MET Determinants from Embryonic Development to Cancer Metastasis

“…Integrin α5 can regulate migration and invasion through the FAK/STAT3/AKT axis, and it also contributes to cell resistance to chemotherapy-related treatment [149]. Moreover, multiple molecules can be observed to regulate cells by crosstalk integrin-related signaling, such as Myosin Heavy Chain 9 (MYH9), Rab11, and Wnt5a [150][151][152], especially the latter, as the paracrine factors involved in EMT/MET have been found to modulate the ITGAV level in ovarian cancer [152]. Interestingly, the interaction of osteopontin and integrin αvβ3 can accelerate cellular uptake of glucose to improve cell migration ability [153].…”