Leading Wnt down a PCP path: Cthrc1 acts as a coreceptor in the Wnt-PCP pathway.
ABSTRACT The Wnt signaling pathway controls myriad developmental events including cell proliferation, migration, patterning, fate, and differentiation. Many Wnt-mediated events are regulated through a canonical pathway in which binding of a Wnt to a Frizzled (Fzd) receptor leads to stabilization of β-catenin. However, in other contexts, Wnt-Fz binding leads to activation of an alternate pathway that acts through a different set of signaling molecules to regulate planar cell polarity (PCP) and related developmental events. PCP refers to the uniform orientation of a particular aspect of a group of cells, usually within an epithelial plane. The most obvious examples of PCP are the orientation of actin-based hairs along the wing and body of Drosophila, the orientation of hair follicles on the vertebrate body and the orientation of mechanosensory hair cells in the mammalian auditory sensory epithelium, the organ of Corti. While a role for wg, the Drosophila homolog of Wnt, in PCP has not been demonstrated, loss of Wnt function clearly disrupts PCP in vertebrates (reviewed in Karner et al., 2006). Results from genetic deletion studies in mice have indicated that specific Wnt and Fzd genes mediate PCP signaling (Wang et al., 2006). However, biochemical studies suggest that Wnt-Fzd interactions may be fairly promiscuous with limited evidence for formation of specific ligand-receptor pairs (reviewed in Kikuchi et al., 2007).
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ABSTRACT: The distinction between dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) is a well-known challenge for dermatopathologists. Immunohistochemical stains have been used to augment routine histological examination to aid in differentiating DF from DFSP. Collagen triple helix repeat containing-1 (Cthrc1) was identified as a novel gene expressed in the adventitia and neointima on arterial injury. It is indicated to be a cell type-specific inhibitor of transforming growth factor-β, which in turn impacts collagen type I and III deposition, neointimal formation, and dedifferentiation of stem cells. Cthrc1 has also been shown to be highly active and potent in degrading extracellular matrix proteins and was found to be overexpressed in several malignant tumours, such as breast cancer and malignant melanoma. To our knowledge, however, expression of Cthrc1 in DFSP and DF has not been studied before. To assess the expression of Cthrc1 in DFSP and DF and to ascertain whether Cthrc1 is superior to antibodies traditionally used in differentiating DF from DFSP. Immunohistochemical staining was performed on 23 cases of DFSP and 35 cases of DF, using antibodies to Cthrc1, CD34, factor XIIIa, CD10 and stromelysin-3 (ST3). Twenty-two of 23 (96%) DFSP samples were positive for Cthrc1, whereas 32 of 35 (91%) DF samples were negative. CD34 was expressed in most DFSPs (22 of 23, 96%), whereas it was completely negative in most cases of DF (29 of 35, 83%). Expression of factor XIIIa was found in most cases of DF (33 of 35, 94%), whereas it was completely absent in 21 of 23 (91%) DFSP cases. Expression of CD10 was found in most cases of DF (30 of 35, 86%), whereas it was completely absent in 13 of 23 (57%) DFSP cases. ST3 was expressed strongly in most cases of DF (32 of 35, 91%), whereas it was completely absent in 18 of 23 (78%) DFSP cases. The preferential Cthrc1 staining of DFSP in comparison with DF was statistically significant (P < 0·01). We confirmed that Cthrc1 is a positive marker for DFSP and that Cthrc1 staining might be more reliable than markers traditionally used. Cthrc1 was not positive in absolutely [corrected] all cases of DFSP, and combination with CD34, factor XIIIa and ST3 immunostaining could make the distinction more reliable.British Journal of Dermatology 01/2011; 164(1):135-40. DOI:10.1111/j.1365-2133.2010.10050.x · 4.10 Impact Factor
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ABSTRACT: Collagen triple helix repeat containing-1 (Cthrc1) was identified as a novel gene expressed in the adventitia and neointima on arterial injury and was found to be overexpressed in several malignant tumours, such as breast cancer and malignant melanoma. However, the expression of Cthrc1 and its role in gastric cancer progression remain unknown. We investigated the expression of the Cthrc1 protein by immunohistochemistry in 30 normal tissues from the control subjects and 166 gastric carcinomas and analyzed its correlation with various clinicopathologic features, including patient outcome. Cthrc1 immunoreactivity was overexpressed in gastric carcinoma cases compared with normal tissues (P < 0.001). High Cthrc1 expression was found in 108 (65.06%) of these 166 carcinomas and was positively correlated with the American Joint Committee on Cancer stage classification, depth of gastric wall invasion, lymph node metastasis, lymph vascular space involvement, and recurrence, but not with age, tumor site and CEA level. Patients with high Cthrc1 expression had significantly poorer overall survival and disease-free survival compared with patients with low expression of Cthrc (P = 0.001 and P = 0.002, respectively). Multivariate analysis showed that high Cthrc1 expression was an independent prognostic factor for both overall survival and disease-free survival of patients with gastric carcinoma (both P = 0.005). These results showed that high Cthrc1 expression was associated with progression and prognosis of gastric carcinoma.Human pathology 05/2014; 45(5). DOI:10.1016/j.humpath.2013.12.020 · 2.81 Impact Factor
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ABSTRACT: Collagen triple helix repeat containing 1 (Cthrc1) has been recently documented in various malignancies, but its role in non-small cell lung cancer (NSCLC) remains uncertain. In the current study, we investigated the level of Cthrc1 in NSCLC tissues by immunohistochemistry. Results revealed that Cthrc1 overexpression was significantly associated with differentiation (P = 0.039), tumor-node-metastasis (TNM) stage (P = 0.035), lymph node status (P = 0.001), and cigarette smoke (P = 0.037). Furthermore, it was shown that patients with high Cthrc1 expression had significantly poorer overall survival (OS) and disease-free survival (DFS; P = 0.004 and P = 0.010, respectively). Interestingly, high Cthrc1 expression was an independent prognostic factor for both OS and DFS (P = 0.010 and P = 0.005, respectively) only in NSCLCs with cigarette smoke. These results indicated and suggested that Cthrc1 could be used as a prognostic marker for NSCLC, and it may play an important role in the smoked-related NSCLC.Tumor Biology 08/2014; 35(11). DOI:10.1007/s13277-014-2449-0 · 3.61 Impact Factor