title: Migration and invasion is inhibited by silencing ROR1 and ROR2 in chemoresistant ovarian cancer.
abstract: Ovarian cancer survival remains poor despite recent advances in our understanding of genetic profiles. Unfortunately, the majority of ovarian cancer patients have recurrent disease after chemotherapy and lack other treatment options. Wnt signalling has been extensively implicated in cancer progression and chemoresistance. Therefore, we investigated the previously described Wnt receptors ROR1 and ROR2 as regulators of epithelial-to-mesenchymal transition (EMT) in a clinically relevant cell line model. The parental A2780- and cisplatin-resistant A2780-cis cell lines were used as a model of ovarian cancer chemoresistance. Proliferation, adhesion, migration and invasion were measured after transient overexpression of ROR1 and ROR2 in the parental A2780 cell line, and silencing of ROR1 and ROR2 in the A2780-cis cell line. Here we show that ROR1 and ROR2 expression is increased in A2780-cis cells, alongside β-catenin-independent Wnt targets. Knockdown of ROR1 and ROR2 significantly inhibited cell migration and invasion and simultaneous knockdown of ROR1 and ROR2 significantly sensitised cells to cisplatin, whilereas ROR overexpression in the parental cell line increased cell invasion. Therefore, ROR1 and ROR2 have the potential as novel drug targets in metastatic and recurrent ovarian cancer patients.
authors.affiliation: Adult Cancer Program, Level 2, Metastasis Research Group, Lowy Cancer Research Centre and School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
authors.forename: C E
authors.initials: CE
authors.lastname: Henry
authors.affiliation: Adult Cancer Program, Level 2, Metastasis Research Group, Lowy Cancer Research Centre and School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Llamosas
authors.affiliation: Adult Cancer Program, Level 2, Metastasis Research Group, Lowy Cancer Research Centre and School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Djordjevic
authors.affiliation: Gynaecological Cancer Centre, Royal Hospital for Women, Sydney and School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
authors.forename: N F
authors.initials: NF
authors.lastname: Hacker
authors.affiliation: Adult Cancer Program, Level 2, Metastasis Research Group, Lowy Cancer Research Centre and School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
authors.forename: C E
authors.initials: CE
authors.lastname: Ford