Epithelial-mesenchymal transition induced by the stromal cell-derived factor-1/CXCR4 system in oral squamous cell carcinoma cells

Onoue, Takeshi; Uchida, Daisuke; Begum, Naseem; Tomizuka, Yoshifumi; Yoshida, Hideo; Sato, Mitsunobu

doi:10.3892/ijo.29.5.1133

Cited by 82 publications

(96 citation statements)

References 21 publications

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“…Our data showed that Vimentin and Slug could be downregulated in CXCR4 knockdown cells. It is consistent with the study on oral carcinomas which showed that CXCR4 could influence EMT formation and cancer invasion (Onoue et al, 2006).…”

Section: Discussionsupporting

confidence: 80%

Blockade of SDF-1/CXCR4 signalling inhibits pancreatic cancer progression in vitro via inactivation of canonical Wnt pathway

et al. 2008

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Extra-pancreatic metastasis is a difficult problem for surgical intervention in pancreatic cancer. CXC chemokine receptor 4 (CXCR4) was considered to have an important role in this process. We hypothesized it may contribute to the pancreatic cancer progression through influencing canonical Wnt pathway. The purpose of this study was to examine the functional role of CXCR4 in the progression of pancreatic cancers and explore the possible mechanism. To this end, the relation between CXCR4 and clinical characteristics was analysed. shRNA against CXCR4 was applied to disrupt the SDF-1/CXCR4 signal transduction pathways in pancreatic cancer cell lines. Our results showed that overall survival in the case of patients positive for CXCR4 expression was significantly lower than that in the case of patients negative for CXCR4 expression. Notably, in vitro studies we observed that the abrogation of CXCR4 could obviously influence the pancreatic cancer cell phenotype including cell proliferation, colony formation, cell invasion and also inhibit the TOPflash activity. In addition, Wnt target genes and mesenchymal markers such as Vimentin and Slug were also inhibited in CXCR4 knockdown cells. Collectively, these data reported here demonstrate CXCR4 could modulate the canonical Wnt pathway and perhaps be a promising therapeutic target for pancreatic cancer progression.

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Section: Discussionsupporting

confidence: 80%

Blockade of SDF-1/CXCR4 signalling inhibits pancreatic cancer progression in vitro via inactivation of canonical Wnt pathway

et al. 2008

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“…As certain reports have suggested the occurrence of radiationinduced EMT (30), we believe that CAFs could be associated with tumor re-growth and distant recurrence in rectal cancer after CRT. In in vitro studies, Onoue et al demonstrated that the SDF-1/CXCR4 axis is involved in EMT in oral squamous cell carcinoma (31). We believe that SDF-1 also strongly contributes to EMT.…”

Section: Discussionmentioning

confidence: 99%

Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy

Saigusa

Toiyama²,

Yokoe³

et al. 2011

Int J Oncol

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Abstract. Cancer-associated fibroblasts (CAFs) in the stroma play an important role in influencing the proliferation, invasion and metastasis of cancer cells. Fibroblast activation protein-α (FAP-α) is known as a marker of CAFs, while stromal cell-derived factor-1 (SDF-1) is primarily expressed by CAFs. Herein, we investigated whether the expression levels of these genes are associated with clinical outcome after pre-operative chemoradiotherapy (CRT) in rectal cancer patients. We obtained total RNA from residual cancer stroma using microdissection from a total of 52 rectal cancer specimens from patients who underwent pre-operative CRT, we performed transcriptional analyses, and the serum protein concentrations in 40 matched microdissected specimens were measured by enzyme-linked immunosorbent assay. Additionally, we sought to clarify the location of FAP-α and SDF-1 expression using immunohistochemical staining. Of the 52 patients, 15.6 and 36.8% showed detectable FAP-α and SDF-1 mRNA expression, respectively. A significant correlation was observed between stromal FAP-α and SDF-1 mRNA levels. Moreover, there was a significant correlation between stromal SDF-1 gene expression levels and serum protein levels. Patients who developed distant recurrences after CRT had positive expression of both genes (P<0.05). The positive expression of both genes was also associated with poor probability of recurrence-free and overall survival (P<0.05). Patients with elevated serum SDF-1 levels had equally poor overall survival as those with positive stromal SDF-1 gene expression (P<0.05). In immunohistochemistry, both FAP-α and SDF-1 expression was observed in certain activated fibroblasts. In conclusion, FAP-α and SDF-1 expression was shown to be involved in tumor re-growth and recurrence in rectal cancer patients treated with pre-operative CRT.

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“…Accumulating evidence indicates that the PI3K/Akt pathway regulates EMT, cell cycle, angiogenesis, and apoptosis (Chandramohan et al 2004, Onoue et al 2006, Fang et al 2007, Cheng et al 2008. Phosphorylated Akt activates mTOR, a major regulator of protein translation.…”

Section: Discussionmentioning

confidence: 99%

miR-145 suppresses thyroid cancer growth and metastasis and targets AKT3

Boufraqech¹,

Zhang²,

Jain³

et al. 2014

Endocrine-Related Cancer

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The expression and function of miR-145 in thyroid cancer is unknown. We evaluated the expression and function of miR-145 in thyroid cancer and its potential clinical application as a biomarker. We found that the expression of miR-145 is significantly downregulated in thyroid cancer as compared with normal. Overexpression of miR-145 in thyroid cancer cell lines resulted in: decreased cell proliferation, migration, invasion, VEGF secretion, and E-cadherin expression. miR-145 overexpression also inhibited the PI3K/Akt pathway and directly targeted AKT3. In vivo, miR-145 overexpression decreased tumor growth and metastasis in a xenograft mouse model, and VEGF secretion. miR-145 inhibition in normal primary follicular thyroid cells decreased the expression of thyroid cell differentiation markers. Analysis of indeterminate fine-needle aspiration samples showed miR-145 had a 92% negative predictive value for distinguishing benign from malignant thyroid nodules. Circulating miR-145 levels were significantly higher in patients with thyroid cancer and showed a venous gradient. Serum exosome extractions revealed that miR-145 is secreted. Our findings suggest that miR-145 is a master regulator of thyroid cancer growth, mediates its effect through the PI3K/Akt pathway, is secreted by the thyroid cancer cells, and may serve as an adjunct biomarker for thyroid cancer diagnosis.

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Epithelial-mesenchymal transition induced by the stromal cell-derived factor-1/CXCR4 system in oral squamous cell carcinoma cells

Cited by 82 publications

References 21 publications

Blockade of SDF-1/CXCR4 signalling inhibits pancreatic cancer progression in vitro via inactivation of canonical Wnt pathway

Blockade of SDF-1/CXCR4 signalling inhibits pancreatic cancer progression in vitro via inactivation of canonical Wnt pathway

Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy

miR-145 suppresses thyroid cancer growth and metastasis and targets AKT3

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