CD44, Sonic Hedgehog, and Gli1 Expression Are Prognostic Biomarkers in Gastric Cancer Patients after Radical Resection

Chen, Jianhui; Zhai, Ertao; Chen, Sile; Wu, Hui; Wu, Ke; Zhang, Xinhua; Chen, Chuangqi; Cai, Shirong; He, Yulong

doi:10.1155/2016/1013045

Cited by 19 publications

(14 citation statements)

References 20 publications

(21 reference statements)

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“…An increasing number of studies have indicated that the Shh pathway is aberrantly activated in several types of cancer and plays a critical role in cancer growth, invasion and metastasis [29][30][31]. Recent studies have demonstrated that the Shh pathway is overactivated in GC, and that it is associated with an aggressive biological behavior [13][14][15]. However, the association between Shh pathway components and the clinicopathological features and prognosis of patients with GC remains contentious.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the ectopic activation of the Shh pathway has been detected in a number of human malignancies [11,12]. Numerous reports have indicated that the Shh pathway plays a crucial role in GC initiation, progression and metastasis, and it has also been shown to be associated with patient prognosis [13][14][15]. Therefore, a deeper understanding of this pathway in tumor invasion and metastasis may provide great promise for GC therapy.…”

Section: Ivyspringmentioning

confidence: 99%

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Sonic Hedgehog/Gli1 Signaling Pathway Regulates Cell Migration and Invasion via Induction of Epithelial-to-mesenchymal Transition in Gastric Cancer

Ke¹,

Wang²,

Liu³

et al. 2020

J. Cancer

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Background:The aberrant activation of the Sonic hedgehog (Shh) signaling pathway is involved in progression of several types of cancer, including gastric cancer (GC). However, it remains uncertain whether it also plays a critical role in promoting cancer initiation and progression by inducing epithelial-to-mesenchymal transition (EMT) in GC. Thus, the aim of the present study was to determine whether the Shh pathway is involved in GC, and to investigate the function of the Shh pathway in the induction of EMT in GC. Materials and methods: The expression levels of Shh pathway members and EMT markers were examined in GC tissues by immunohistochemistry. The association between these factors and patient clinicopathological characteristics was analyzed. In addition, Gli-antagonist 61 (GANT61) was used to block Shh/Gli1 pathway activity, and recombinant Shh proteins (N-Shh) were used to activate the Shh pathway in GC cells. Wound healing and Transwell invasion and migration assays were performed to assess the effects of the Shh pathway on the migration and invasion of GC cells in vitro. Furthermore, western blot analysis was used to examine the changes in protein expression. Results: The results demonstrated that these Shh/Gli1 pathway members were upregulated in GC tissues, and that Gli1 upregulation was associated with tumor progression and a poor prognosis. Gli1 expression was negatively associated with E-cadherin (E-Cad) expression, and positively with Vimentin (VIM) expression in GC specimens. Further analysis revealed that when the Shh/Gli1 pathway was activated, the migratory and invasive abilities of GC cells were enhanced, and the expression levels of Gli1 and VIM were increased, while E-Cad expression was decreased. Opposite results were observed when the Shh/Gli1 pathway was blocked by GANT61. Conclusions: The present study indicated that the Shh/Gli1 pathway exhibits an abnormal activation pattern in GC with possible predictive and prognostic significance. The Shh/Gli1 pathway may promote the migratory and invasive potential of GC cells by inducing EMT. The Shh/Gli1 pathway can thus be considered as a potential therapeutic target for GC.

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Section: Discussionmentioning

confidence: 99%

Section: Ivyspringmentioning

confidence: 99%

Sonic Hedgehog/Gli1 Signaling Pathway Regulates Cell Migration and Invasion via Induction of Epithelial-to-mesenchymal Transition in Gastric Cancer

Ke¹,

Wang²,

Liu³

et al. 2020

J. Cancer

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“…Mayer et al and Jian-Hui et al indicated that higher expression of total CD44 is associated with a greater possibility of distant metastasis and higher TNM stages [18,41]. CD44v6, one of the major variants of CD44, plays an important biological role in tumor invasion and metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…Of the 42 studies that were used for the meta-analysis, total CD44 was reported in 21 papers [5,16,18,20,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] and CD44v6 expression in 24 studies [17,19,21,22,24,28,37,[42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57]. The main characteristics of these studies are summarized in Table 1 and Table 2.…”

Section: Description Of Eligible Literaturementioning

confidence: 99%

CD44 and CD44v6 are Correlated with Gastric Cancer Progression and Poor Patient Prognosis: Evidence from 42 Studies

Fang

Lai³

et al. 2016

Cell Physiol Biochem

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Background/Aims: The prognostic power of the levels of total CD44 and its isoform CD44v6 for patients with gastric cancer (GC) remains controversial. Therefore, our study aims to generalize the clinicopathological and prognostic significance of these two proteins in GC. Methods: A literature search of the PubMed, Web of Science and Embase databases was conducted to identify eligible studies. The odds ratio (OR) with a 95% confidence interval (CI) was used to assess the effects. Results: In all, 42 studies including 6,229 patients were included in this analysis. Total CD44 was mentioned in 21 papers, and the results showed that CD44 was positively correlated with the T category, the N category, distant metastasis, lymphatic invasion and TNM stage. Moreover, patients with CD44 overexpression had a lower 5-year overall survival (OS) rate (OR = 3.35, 95%CI = 1.83-6.13). CD44v6 was mentioned in 24 studies, with results that were similar to those for total CD44. However, total CD44 or CD44v6 expression was not correlated with tumor size and histological grade. Conclusion: High CD44 or CD44v6 expression levels were correlated with cancer progression and poor prognosis in patients with GC. Both CD44 and CD44v6 may be useful diagnostic or prognostic biomarkers for GC.

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“…Notably, the role of gli1 as a proto-oncogene driving basal cell carcinoma, was proposed based on Xenopus data, then confirmed in mouse cancer models and finally in cancer patients [28, 29]. The contributions made in Xenopus resulted in gli1 being used as a prognostic biomarker for the disease, underlying how basic research in lower animals can impact human health [30]. …”

Section: Integrating Nonmammalian Models For Studying Defenses Againsmentioning

confidence: 99%

Tumor Immunology Viewed from Alternative Animal Models—the Xenopus Story

Banach

Robert

2017

Curr Pathobiol Rep

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a) Purpose of review Nonmammalian comparative animal models are important not only to gain fundamental evolutionary understanding of the complex interactions of tumors with the immune system, but also to better predict the applicability of novel immunotherapeutic approaches to humans. After reviewing recent advances in developing alternative models, we focus on the amphibian Xenopus laevis and its usefulness in deciphering the perplexing roles of MHC class I-like molecules and innate (i)T cells in tumor immunity. b) Recent findings Experiments using MHC-defined inbred and cloned animals, tumor cell lines, effective reagents, sequenced genomes, and adapted gene editing techniques in Xenopus, have revealed that the critical involvement of class I-like molecules and iT cells in tumor immunity has been conserved during evolution. c) Summary Comparative studies with the X. laevis tumor immunity model can contribute to the development of better and more efficient cancer immunotherapies.

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CD44, Sonic Hedgehog, and Gli1 Expression Are Prognostic Biomarkers in Gastric Cancer Patients after Radical Resection

Cited by 19 publications

References 20 publications

Sonic Hedgehog/Gli1 Signaling Pathway Regulates Cell Migration and Invasion via Induction of Epithelial-to-mesenchymal Transition in Gastric Cancer

Sonic Hedgehog/Gli1 Signaling Pathway Regulates Cell Migration and Invasion via Induction of Epithelial-to-mesenchymal Transition in Gastric Cancer

CD44 and CD44v6 are Correlated with Gastric Cancer Progression and Poor Patient Prognosis: Evidence from 42 Studies

Tumor Immunology Viewed from Alternative Animal Models—the Xenopus Story

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