Diagnostic investigations of DKK‐1 and PDCD5 expression levels as independent prognostic markers of human chondrosarcoma

Zarea, Mojtaba; Bajgiran, Amirhossein Mohammadian; Sedaghati, Farnoush; Hatami, Negin; Taheriazam, Afshin; Yahaghi, Emad; Shakeri, Mohammadreza

doi:10.1002/iub.1519

Cited by 4 publications

(4 citation statements)

References 29 publications

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“…We hypothesize that this inactivation could be explained, at least in part, by the high levels of several Wnt antagonists, such as DKK-1, DKK-3 and/or DKK-4. DKK-1 in particular has been found to be overexpressed in a plethora of tumors with a clear oncogenic function [ 17 , 18 , 19 ]. In this context, it has been demonstrated that the reactivation of the Wnt/β-catenin pathway by Glycogen synthase kinase 3 inhibitors has anti-oncogenic effects in RMS [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Dickkopf-1 Inhibition Reactivates Wnt/β-Catenin Signaling in Rhabdomyosarcoma, Induces Myogenic Markers In Vitro and Impairs Tumor Cell Survival In Vivo

Giralt

Gallo-Oller

Navarro

et al. 2021

IJMS

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The Wnt/β-catenin signaling pathway plays a pivotal role during embryogenesis and its deregulation is a key mechanism in the origin and progression of several tumors. Wnt antagonists have been described as key modulators of Wnt/β-catenin signaling in cancer, with Dickkopf-1 (DKK-1) being the most studied member of the DKK family. Although the therapeutic potential of DKK-1 inhibition has been evaluated in several diseases and malignancies, little is known in pediatric tumors. Only a few works have studied the genetic inhibition and function of DKK-1 in rhabdomyosarcoma. Here, for the first time, we report the analysis of the therapeutic potential of DKK-1 pharmaceutical inhibition in rhabdomyosarcoma, the most common soft tissue sarcoma in children. We performed DKK-1 inhibition via shRNA technology and via the chemical inhibitor WAY-2626211. Its inhibition led to β-catenin activation and the modulation of focal adhesion kinase (FAK), with positive effects on in vitro expression of myogenic markers and a reduction in proliferation and invasion. In addition, WAY-262611 was able to impair survival of tumor cells in vivo. Therefore, DKK-1 could constitute a molecular target, which could lead to novel therapeutic strategies in RMS, especially in those patients with high DKK-1 expression.

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Section: Discussionmentioning

confidence: 99%

Dickkopf-1 Inhibition Reactivates Wnt/β-Catenin Signaling in Rhabdomyosarcoma, Induces Myogenic Markers In Vitro and Impairs Tumor Cell Survival In Vivo

Giralt

Gallo-Oller

Navarro

et al. 2021

IJMS

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“…In many tumors, DKK-1 clearly acts only as an oncogene ( Supplementary Table S1 ). For instance, several studies showed a relationship between DKK-1 overexpression and worse prognosis in common tumors such as lung cancer (including non-small cell lung cancer) [ 27 , 28 ] and rare malignancies such as chondrosarcoma [ 29 , 30 ]. However, the setting is highly complex and a clear oncogenic or anti-oncogenic role of DKK-1 in a given tumor type is not always clear, with a plethora of examples in which references to both sides may be found.…”

Section: The Dickkopf (Dkk) Family and Its Role In Cancermentioning

confidence: 99%

Dickkopf Proteins and Their Role in Cancer: A Family of Wnt Antagonists with a Dual Role

et al. 2021

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The Wnt signaling pathway regulates crucial aspects such as cell fate determination, cell polarity and organogenesis during embryonic development. Wnt pathway deregulation is a hallmark of several cancers such as lung, gastric and liver cancer, and has been reported to be altered in others. Despite the general agreement reached by the scientific community on the oncogenic potential of the central components of the pathway, the role of the antagonist proteins remains less clear. Deregulation of the pathway may be caused by overexpression or downregulation of a wide range of antagonist proteins. Although there is growing information related to function and regulation of Dickkopf (DKK) proteins, their pharmacological potential as cancer therapeutics still has not been fully developed. This review provides an update on the role of DKK proteins in cancer and possible potential as therapeutic targets for the treatment of cancer; available compounds in pre-clinical or clinical trials are also reviewed.

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“…indicated the upregulation of Oct‐4 was upregulated in metaplastic pancreatic ducts compared with normal acini and pancreatic carcinoma. Furthermore, many markers for early diagnosis of the various cancers earlier have conducted . Therefore, this study was aimed to investigate the clinical significance of MUC5AC and Oct‐4 expression in patients with GC in an Iranian population.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, many markers for early diagnosis of the various cancers earlier have conducted. [15][16][17] Therefore, this study was aimed to investigate the clinical significance of MUC5AC and Oct-4 expression in patients with GC in an Iranian population.…”

Section: Introductionmentioning

confidence: 99%

Differential expression of two genes Oct‐4 and MUC5AC associates with poor outcome in patients with gastric cancer

Javanbakht

Akhavan-Moghadam

Talaei

et al. 2017

Clin Exp Pharma Physio

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Gastric cancer (GC) is the most frequent leading cause of cancer-associated mortality worldwide that is linked to poor prognosis due to the lack of appropriate biomarkers. Our aim was to evaluate the MUC5AC and Oct-4 expression levels in GC and to assess their association with clinical factors. Immunohistochemical analysis (IHC) and qRT-PCR were performed in GC patients to examine the MUC5AC and Oct-4 expression levels. The mRNA level of MUC5AC was significantly decreased in tumour tissues compared with non-cancerous tissues (1.11 ± 0.69 vs 3.7 ± 0.71; P = .024). On the other hand, Oct-4 mRNA level was upregulated in tumour tissues as compared to normal tissues (2. 86 ± 0.78 vs 0.87 ± 0.54; P = .0015). Decreased expression of MUC5AC was detected in 27 patients (67.5%), while high to moderate expression levels were observed in 13 cases (32.5%), but in normal tissues the expression levels of MUC5AC were increased (P = .001). The decreased expression of MUC5AC was associated with aggressive tumour characteristics, such as TNM stage (P = .023), histologic type (P = .012) and lymph node metastasis (P = .001). High expression of Oct-4 was detected in 24 tumour tissues (60%), while 16 cases (40%) showed low expression level. Increased Oct-4 expression was correlated with clinicopathological characteristics such TNM stage (P = .002), histologic type (P = .008) and lymph node metastasis (P = .001). Our results showed that high Oct-4 expression and the reduction of MUC5AC expression may be involved in the progression and an unfavorable prognosis of GC.

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Diagnostic investigations of DKK‐1 and PDCD5 expression levels as independent prognostic markers of human chondrosarcoma

Cited by 4 publications

References 29 publications

Dickkopf-1 Inhibition Reactivates Wnt/β-Catenin Signaling in Rhabdomyosarcoma, Induces Myogenic Markers In Vitro and Impairs Tumor Cell Survival In Vivo

Dickkopf-1 Inhibition Reactivates Wnt/β-Catenin Signaling in Rhabdomyosarcoma, Induces Myogenic Markers In Vitro and Impairs Tumor Cell Survival In Vivo

Dickkopf Proteins and Their Role in Cancer: A Family of Wnt Antagonists with a Dual Role

Differential expression of two genes Oct‐4 and MUC5AC associates with poor outcome in patients with gastric cancer

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