A ROS/STAT3/HIF-1α signaling cascade mediates EGF-induced TWIST1 expression and prostate cancer cell invasion

Cho, Kyung Hwa; Choi, Moonjung; Jeong, Kang Jin; Kim, Jeong Jin; Hwang, M. H.; Shin, Shang Cheul; Park, Chang Gyo; Lee, Hoi Young

doi:10.1002/pros.22776

Cited by 80 publications

(52 citation statements)

References 30 publications

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“…Although we have previously reported the constitutive activation of HIF-1α in normoxic cancer cells with a stable MDR phenotype [30], the parallel increase in HIF-1α transcription and the progressive acquisition of MDR is a new observation. This trend may be due to the use of doxorubicin as selective agent: indeed, in normoxia the drug produces reactive oxygen species [31] that increase HIF-1α [32]. During the onset of the MDR phenotype, the increase of HIF-1α was paralleled by an increase of CAXII and Pgp mRNAs.…”

Section: Discussionmentioning

confidence: 99%

Carbonic anhydrase XII is a new therapeutic target to overcome chemoresistance in cancer cells

et al. 2015

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Multidrug resistance (MDR) in cancer cells is a challenging phenomenon often associated with P-glycoprotein (Pgp) surface expression. Finding new ways to bypass Pgp-mediated MDR still remains a daunting challenge towards the successful treatment of malignant neoplasms such as colorectal cancer.We applied the Cell Surface Capture technology to chemosensitive and chemoresistant human colon cancer to explore the cell surface proteome of Pgp-expressing cells in a discovery-driven fashion. Comparative quantitative analysis of identified cell surface glycoproteins revealed carbonic anhydrase type XII (CAXII) to be up-regulated on the surface of chemoresistant cells, similarly to Pgp. In cellular models showing an acquired MDR phenotype due to the selective pressure of chemotherapy, the progressive increase of the transcription factor hypoxia-inducible factor-1 alpha was paralleled by the simultaneous up-regulation of Pgp and CAXII. CAXII and Pgp physically interacted at the cell surface. CAXII silencing or pharmacological inhibition with acetazolamide decreased the ATPase activity of Pgp by altering the optimal pH at which Pgp operated and promoted chemosensitization to Pgp substrates in MDR cells.We propose CAXII as a new secondary marker of the MDR phenotype that influences Pgp activity directly and can be used as a pharmacological target for MDR research and potential treatment.

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Section: Discussionmentioning

confidence: 99%

Carbonic anhydrase XII is a new therapeutic target to overcome chemoresistance in cancer cells

et al. 2015

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“…Several lines of evidence have demonstrated that EGF can induce EMT in various types of cancer cells, including breast cancer [30], prostate cancer [31, 32], cervical cancer [33], and head and neck cancer [22, 34]. Meanwhile, EGF stimulation endows head and neck cancer cells with stem-like cell properties [22].…”

Section: Introductionmentioning

confidence: 99%

EGF induces epithelial-mesenchymal transition and cancer stem-like cell properties in human oral cancer cells via promoting Warburg effect

Zhang

Ishida

et al. 2016

Oncotarget

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“Warburg effect”, the enhanced glycolysis or aerobic glycolysis, confers cancer cells the ability to survive and proliferate even under stressed conditions. In this study, we explored the role of epidermal growth factor (EGF) in orchestrating Warburg effect, the epithelial-mesenchymal transition (EMT) process, and the acquisition of cancer stem-like cell properties in human oral squamous cell carcinoma (OSCC) cells. Our results showed that EGF induces EMT process in OSCC cells, which correlates with the acquisition of cancer stem-like properties, including the enrichment of CD44+/CD24− population of cancer cells and an increased expression of CSC-related genes, aldehyde dehydrogenase-1 (ALDH1) and Bmi-1. We also showed that EGF concomitantly enhanced L-lactate production, while blocking glycolysis by 2-deoxy-D-glucose (2-DG) robustly reversed EGF-induced EMT process and CSC-like properties in OSCC cells. Mechanistically, we demonstrated that EGF promoted EMT process and CSC generation through EGFR/PI3K/HIF-1α axis-orchestrated glycolysis. Using an orthotopic tumor model of human OSCC (UM-SCC1) injected in the tongue of BALB/c nude mice, we showed that treatment with 2-DG in vivo significantly inhibited the metastasis of tumor cells to the regional cervical lymph nodes and reduced the expression of ALDH1 and vimentin in both in situ tumors and tumor cell-invaded regional lymph nodes. Taken together, these findings have unveiled a new mechanism that EGF drives OSCC metastasis through induction of EMT process and CSC generation, which is driven by an enhanced glycolytic metabolic program in OSCC cells.

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“…Cell migration is a dynamic, wellorganized and complex process requiring co-ordination of many molecules in cells. Numerous studies have demonstrated that EGF activates its receptor, following resulting in increased cell migration in human tumorous cells (Cho et al, 2014;Jeong et al, 2014;Magi et al, 2014), thus EGF, via its receptor, plays an important role in cell migration and tumor invasion. Our research, using in vitro wound healing assay, clearly showed that EGF induced human cervical cancer SiHa cell migration (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

Aquaporin 8 Involvement in Human Cervical Cancer SiHa Migration via the EGFR-Erk1/2 Pathway

Shi¹,

Tuokan²,

Chen³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Overexpression of aquaporins (AQPs) has been reported in several human cancers. Epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinases 1/2 (Erk1/2) are associated with tumorigenesis and cancer progression and may upregulate AQP expression. In this study, we demonstrated that EGF (epidermal growth factor) induces SiHa cells migration and AQP8 expression. Wound healing results showed that cell migration was increased by 2.79-1.50-fold at 24h and 48h after EGF treatment. AQP8 expression was significantly increased (3.33-fold) at 48h after EGF treatment in SiHa cells. An EGFR kinase inhibitor, PD153035, blocked EGFinduced AQP8 expression and cell migration and AQP8 expression was decreased from 1.59-fold (EGF-treated) to 0.43-fold (PD153035-treated) in SiHa. Furthermore, the MEK (MAPK (mitogen-activated protein kinase)/ Erk (extracellular signal regulated kinase)/Erk inhibitor U0126 also inhibited EGF-induced AQP8 expression and cell migration. AQP8 expression was decreased from 1.21-fold (EGF-treated) to 0.43-fold (U0126-treated). Immunofluorescence microscopy further confirmed the results. Collectively, our findings show that EGF induces AQP8 expression and cell migration in human cervical cancer SiHa cells via the EGFR/Erk1/2 signal transduction pathway.

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A ROS/STAT3/HIF-1α signaling cascade mediates EGF-induced TWIST1 expression and prostate cancer cell invasion

Abstract: We demonstrate a mechanism by which EGF promotes prostate cancer cell progression through a ROS/STAT3/HIF-1α/TWIST1/N-cadherin signaling cascade, providing novel biomarkers and promising therapeutic targets for prostate cancer cell progression.

Cited by 80 publications

References 30 publications

Carbonic anhydrase XII is a new therapeutic target to overcome chemoresistance in cancer cells

Carbonic anhydrase XII is a new therapeutic target to overcome chemoresistance in cancer cells

EGF induces epithelial-mesenchymal transition and cancer stem-like cell properties in human oral cancer cells via promoting Warburg effect

Aquaporin 8 Involvement in Human Cervical Cancer SiHa Migration via the EGFR-Erk1/2 Pathway

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