The signaling pathways activated by ROR1 in cancer.

The receptor tyrosine kinase orphan receptor 1 (ROR1) is a receptor for WNT5A and related Wnt proteins, that play an important role during embryonic development by regulating cell migration, cell polarity, neural patterning, and organogenesis. ROR1 exerts these functions by transducing signals from the Wnt secreted glycoproteins to the intracellular Wnt/PCP and Wnt/Ca pathways. Investigations in adult human cells, particularly cancer cells, have demonstrated that besides these two pathways, the WNT5A/ROR1 axis can activate a number of signaling pathways, including the PI3K/AKT, MAPK, NF-κB, STAT3, and Hippo pathways.

Bcl-2-like protein-10 increases aggressive features of melanoma cells.

Aim: B-cell lymphoma-2 (Bcl-2)-like protein-10 (Bcl2L10) is the less studied member of Bcl-2 family proteins, with the controversial role in different cancer histotypes. Very recently, Bcl2L10 expression in melanoma tumor specimens and its role in melanoma response to therapy have been demonstrated. Here, the involvement of Bcl2L10 on the and properties associated with melanoma aggressive features has been investigated.

Bioinformatic analysis identifies epidermal development genes that contribute to melanoma progression.

Several diagnostic and prognostic markers for melanoma have been identified in last few years. However, their actual contribution to melanoma progression have not been investigated in detail. This study was aimed to identify genes, biological processes, and signaling pathways implicated in melanoma progression by applying bioinformatics analysis.

ROR2 promotes epithelial-mesenchymal transition by hyperactivating ERK in melanoma.

Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a protein with important functions during embryogenesis that is dysregulated in human cancer. An intriguing feature of this receptor is that it plays opposite roles in different tumor types either promoting or inhibiting tumor progression. Understanding the complex role of this receptor requires a more profound exploration of both the altered biological and molecular mechanisms.

ROR2 increases the chemoresistance of melanoma by regulating p53 and Bcl2-family proteins via ERK hyperactivation.

Background: ROR2 is a tyrosine-kinase receptor whose expression is dysregulated in many human diseases. In cancer, ROR2 stimulates proliferation, survival, migration, and metastasis, and is associated with more aggressive tumor stages. The purpose of this work is to study the role of ROR2 in the chemoresistance of melanoma.

ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation.

Background: Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a Wnt5a receptor aberrantly expressed in cancer that was shown to either suppress or promote carcinogenesis in different tumor types. Our goal was to study the role of ROR2 in melanoma.

Methods: Gain and loss-of-function strategies were applied to study the biological function of ROR2 in melanoma.

BCL2L10 Is Overexpressed in Melanoma Downstream of STAT3 and Promotes Cisplatin and ABT-737 Resistance.

The anti-apoptotic proteins from the Bcl-2 family are important therapeutic targets since they convey resistance to anticancer regimens. Despite the suspected functional redundancy among the six proteins of this subfamily, both basic studies and therapeutic approaches have focused mainly on BCL2, Bcl-xL, and MCL1. The role of BCL2L10, another member of this group, has been poorly studied in cancer and never has been in melanoma.

An Autocrine Wnt5a Loop Promotes NF-κB Pathway Activation and Cytokine/Chemokine Secretion in Melanoma.

Wnt5a signaling has been implicated in the progression of cancer by regulating multiple cellular processes, largely migration and invasion, epithelial-mesenchymal transition (EMT), and metastasis. Since Wnt5a signaling has also been involved in inflammatory processes in infectious and inflammatory diseases, we addressed the role of Wnt5a in regulating NF-κB, a pivotal mediator of inflammatory responses, in the context of cancer. The treatment of melanoma cells with Wnt5a induced phosphorylation of the NF-κB subunit p65 as well as IKK phosphorylation and IκB degradation.

STAT3 enhances the constitutive activity of AGC kinases in melanoma by transactivating PDK1.

Background: The PI3K/Akt and the STAT3 pathways are functionally associated in many tumor types. Both in vitro and in vivo studies have revealed that either biochemical or genetic manipulation of the STAT3 pathway activity induce changes in the same direction in Akt activity. However, the implicated mechanism has been poorly characterized.

A Minimalist Approach to the Design of Complexity-Enriched Bioactive Small Molecules: Discovery of Phenanthrenoid Mimics as Antiproliferative Agents.

Over the last decades, much effort has been devoted to the design of the "ideal" library for screening, the most promising strategies being those which draw inspiration from biogenic compounds, as the aim is to add biological relevance to such libraries. On the other hand, there is a growing understanding of the role that molecular complexity plays in the discovery of new bioactive small molecules. Nevertheless, the introduction of molecular complexity must be balanced with synthetic accessibility.