Wnt/PCP Signaling Contribution to Carcinoma Collective Cell Migration and Metastasis

Abstract

Our understanding of the cellular mechanisms governing carcinoma invasiveness and metastasis has evolved dramatically over the last several years. The previous emphasis on the epithelial-mesenchymal transition as a driver of the migratory properties of single cells has expanded with the observation that carcinoma cells often invade and migrate collectively as adherent groups. Moreover, recent analyses suggest that circulating tumor cells within the vasculature often exist as multicellular clusters and that clusters more efficiently seed metastatic lesions than single circulating tumor cells. While these observations point to a key role for collective cell migration in carcinoma metastasis, the molecular mechanisms driving collective tumor cell migration remain to be discerned. Wnt/PCP (planar cell polarity) signaling, one of the noncanonical Wnt signaling pathways, mediates collective migratory events such as convergent extension during developmental processes. Wnt/PCP signaling components are frequently dysregulated in solid tumors, and aberrant pathway activation contributes to tumor cell migratory properties. Here we summarize key studies that address the mechanisms by which Wnt/PCP signaling mediate collective cell migration in developmental and tumor contexts. We emphasize Wnt/PCP component localization within migrating cells and discuss how component asymmetry may govern the spatiotemporal control of downstream cytoskeletal effectors to promote collective cell motility.

Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis

“…Signatures of collective migration have been noticed clinically as tumor buds – the clusters of undifferentiated cells mainly in the invasive front of a tumor [ 10 ]. As the signatures specific to CTC clusters have begun to being unravelled [ [11] , [12] , [13] ], recent efforts have identified some key signaling pathways that can mediate collective migration during metastasis: Wnt/Planar Cell Polarity (PCP) [ 14 ], Notch-Jagged signaling [ 8 , 15 ] and HIF-1α signaling [ 16 ]. Cell surface molecules such as podocalyxin and plakoglobin can mediate collective cell migration in breast cancer [ 7 , 17 ].…”

Upregulation of Prickle2 Ameliorates Alzheimer’s Disease-Like Pathology in a Transgenic Mouse Model of Alzheimer’s Disease

“…Recently, Wnt/PCP signaling, which participates in development and a variety of human diseases (Katoh, 2005;Chen et al, 2018;Humphries and Mlodzik, 2018), is also associated with a higher risk of AD (Elliott et al, 2018;Sellers et al, 2018). Wnt/PCP signaling contains upstream canonical Wnt signaling pathway components, such as Wnt5A, Wnt5B, and Wnt11, for the transduction of Wnt/PCP signals, followed by several transmembrane protein receptors of the PCP core components, Frizzled (FZD), Dishevelled (DSH), Vangl (van Gogh-like) and the cytoplasmic regulator Prickle (Katoh, 2005;Barrow, 2006;VanderVorst et al, 2019). Most recently, intriguing studies have implicated the involvement of Prickle2 in the pathogenesis of nervous system diseases.…”

OIP5-AS1 contributes to tumorigenesis in hepatocellular carcinoma by miR-300/YY1-activated WNT pathway

“…l The apoptosis of indicated cells was examined by caspase-3 activity analysis. **P < 0.01 Polarity (PCP) pathway has also been studied in recent years due to its role in controlling cancer cell functions [51][52][53]. Current study determined the activation of OIP5-AS1/miR-300/YY1 feedback loop on canonical WNT pathway.…”

“…WNT signaling pathway is complicated and developing, which could contribute to the progression of human cancers. Except for canonical WNT pathway, WNT/Planar Cell Polarity (PCP) pathway has also been studied in recent years due to its role in controlling cancer cell functions [ 51 – 53 ]. Current study determined the activation of OIP5-AS1/miR-300/YY1 feedback loop on canonical WNT pathway.…”