ROR1 contributes to melanoma cell growth and migration by regulating N‐cadherin expression via the PI3K/Akt pathway

Abstract

The Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1) is primarily expressed by neural crest cells during embryogenesis. Following a complete downregulation after birth, ROR1 was shown to re-express in various types of cancers. Little is known about ROR1 expression and function in melanoma. Here we show that ROR1 is aberrantly expressed in both melanoma cell lines and tumors and that its expression associates with poor Post-Recurrence Survival of melanoma. Using gain- and loss-of-function approaches we found that ROR1 enhances both anchorage-dependent and -independent growth of melanoma cells. In addition, ROR1 decreases cell adhesion and increases cell motility and migration. Mechanistically, ROR1 was found to induce upregulation of Akt and the mesenquimal markers N-cadherin and vimentin. The regulation of N-cadherin by ROR1 relies on both Akt dependent and independent mechanisms. ROR1 does not affect Wnt canonical pathway but was found to be engaged in a positive feedback loop with Wnt5a. In summary, we show that ROR1 contributes to melanoma progression and is a candidate biomarker of poor prognosis. Although further studies are needed to confirm this possibility, the present work indicates that ROR1 is a good prospective target for melanoma cancer therapy. © 2015 Wiley Periodicals, Inc.

High-level ROR1 associates with accelerated disease progression in chronic lymphocytic leukemia

“…23 To date, high-level expression of ROR1 has been found to have adverse prognostic significance for patients with breast cancer, [24][25][26][27] ovarian cancer, 28,29 melanoma, 30 or Ewing sarcoma. 31 Moreover, high-level expression of ROR1 also has been associated with higher levels of AKT activation, 24,30,32,33 consistent with the notion that ROR1 signaling leading to activation of AKT may serve as a driver, not just in CLL, but also in other malignancies. Because of this and its restricted postpartum expression, ROR1 may be an attractive target for therapy with either mAbs, 7,34 or other agents that specifically inhibit this orphan receptor and/or its downstream signaling pathways.…”

ROR1 expression as a biomarker for predicting prognosis in patients with colorectal cancer

“…Mechanistically, ROR1 regulates expression of epithelial-mesenchymal transition (EMT) genes, such as SNAIL-1/2, E-cadherin, N-cadherin and vimentin [15, 31]. Silencing ROR1 expression in melanoma significantly inhibits cell migration and invasion through decreasing expression of vimentin and N-cadherin [32]. In our study, we also found a significant association between ROR1 expression and lymph node metastasis, which indicated that ROR1 may also be involved in the process of CRC metastasis.…”

CLCA2 epigenetic regulation by CTBP1, HDACs, ZEB1, EP300 and miR‐196b‐5p impacts prostate cancer cell adhesion and EMT in metabolic syndrome disease

“…Cell adhesion assay was performed as described previously with some modifications . Briefly, after transfections, cells were attached to 96‐well plate for 30 min.…”