Role of Sulf1A in Wnt1‐ and Wnt6‐induced growth regulation and myoblast hyper‐elongation

Abstract

Sulf1A expression, which is a characteristic of embryonic muscle, is undetectable in mature muscle fibres and quiescent satellite cells, but is re-activated in vivo upon injury and in vitro following activation of satellite cells. Sulf1A is known to enhance canonical Wnt signalling, and its association with Wnt1-induced satellite cell proliferation in vitro in the present study further confirmed this. However, exogenous Wnt6 decreased satellite cell proliferation but promoted the adoption of a hyper-elongated cell morphology in myoblasts on isolated single fibres in culture. Such Wnt6-induced cellular hyper-elongation and inhibition of proliferation was found to be dependent upon Sulf1A, as treatment with Sulf1A neutralising antibodies abolished both these effects. This indicates that Sulf1A can regulate Wnt6 signalling and cellular differentiation in skeletal muscle.

Expression of Sulf1 and Sulf2 in cartilage, bone and endochondral fracture healing

“…Osteoblasts prepared from cancellous and subchondral bone showed mainly full length Sulf1 and Sulf2 although a very low level expression of Sulf2 with 240bp exon 6 deletion was also detected in a number of these samples that was not significantly different in cancellous versus subchondral or during 3 hour incubation with 1µM PGE2. This is compatible with little or no expression of such variants in most postnatal tissues except during acute injury compared with fetal (Gill et al 2010;Hitchins et al 2013) and particularly tumour tissues (Gill et al 2014). The requirement of only a very subtle change in the levels of shorter variants, not quantifiable by this method, or proximity to the hypertrophic chondrocytes expressing high levels of full length SULF2, which has been described to have some pro-angiogenic function (Morimoto-Tomita et al 2005), may be sufficient to promote angiogenesis in sub-chondral bone.…”

SULF1/SULF2 reactivation during liver damage and tumour growth

“…The Sulf1/Sulf2 up-regulation, however, was not restricted to only tumour growth but also activated during liver damage induced-liver repair/regeneration during HCC-preceding stages. This study thus supports a hypothesis that Sulf1/Sulf2 activation relates to not only increased cell-signalling during normal development and regeneration (Gill et al 2010;Hitchins et al 2013) but also during abnormal in vivo and in vitro growth. This is further confirmed by Sulf1 and Sulf2 induced in vitro growth promotion of liver tumour cell lines.…”

“…The present study demonstrated the down-regulation of both Sulf1 and Sulf2 in normal adult liver following high levels of their expression during fetal development promoting growth-related active cell signalling. This is compatible with increased expression of Sulfs during fetal development of many tissues (Gill et al 2010;Hitchins et al 2013) and during the development of different tumour types (Gill et al 2012;Gill et al 2014;Lemjabbar-Alaoui et al). It, however, differs from some other studies reporting Sulf1 to be a tumour suppressor in liver (Lai et al 2006;Lai et al 2008a;Xu G et al 2014) thus implying higher level of expression in normal adult liver although some other adult tissues such as neuronal and skeletal tissues have been reported to continue expressing Sulf1/Sulf2 throughout life (Joy et al 2015;Zaman et al 2016).…”

Secreted Frizzled-Related Protein 3 (SFRP3) Is Required for Tumorigenesis of PAX3–FOXO1-Positive Alveolar Rhabdomyosarcoma

“…Interestingly, APC (which promotes the degradation of β-catenin) was also downregulated by the shRNAs, but just missed the threshold of inclusion. Conversely, we noted upregulation of genes including CCND1 (cyclin D1) and SNAI2 (SLUG), both Wnt signaling target genes (39, 40) and WNT6 , which is known to inhibit myoblast proliferation but induce myoblast elongation (41). Taken together, these results suggest that suppression of SFRP3 in part activates β-catenin/Wnt signaling pathway as we had seen in the tumor xenografts.…”