Cancers, Vol. 12, Pages 853: The Core-Clock Gene NR1D1 Impacts Cell Motility in Vitro and Invasiveness in A Zebrafish Xenograft Colon Cancer Model
Cancers, Vol. 12, Pages 853: The Core-Clock Gene NR1D1 Impacts Cell Motility in Vitro and Invasiveness in A Zebrafish Xenograft Colon Cancer Model
Cancers doi: 10.3390/cancers12040853
Authors:
Alireza Basti
Rita Fior
Müge Yalҫin
Vanda Póvoa
Rosario Astaburuaga
Yin Li
Julian Naderi
Miguel Godinho Ferreira
Angela Relógio
Malfunctions of circadian clock trigger abnormal cellular processes and influence tumorigenesis. Using an in vitro and in vivo xenograft model, we show that circadian clock disruption via the downregulation of the core-clock genes BMAL1, PER2, and NR1D1 impacts the circadian phenotype of MYC, WEE1, and TP53, and affects proliferation, apoptosis, and cell migration. In particular, both our in vitro and in vivo results suggest an impairment of cell motility and a reduction in micrometastasis formation upon knockdown of NR1D1, accompanied by altered expression levels of SNAI1 and CD44. Interestingly we show that differential proliferation and reduced tumour growth in vivo may be due to the additional influence of the host-clock and/or to the 3D tumour architecture. Our results raise new questions concerning host–tumour interaction and show that core-clock genes are involved in key cancer properties, including the regulation of cell migration and invasion by NR1D1 in zebrafish xenografts.
Source: Cancers - Category: Cancer & Oncology Authors: Alireza Basti Rita Fior M üge Yalҫin Vanda P óvoa Rosario Astaburuaga Yin Li Julian Naderi Miguel Godinho Ferreira Angela Rel ógio Tags: Article Source Type: research