<scp>MTA</scp>1 drives malignant progression and bone metastasis in prostate cancer

Kumar, Avinash; Dhar, Swati; Butt, Nasir A.; Schallheim, Jason; Gómez, Christian R.; Levenson, Anait S.

doi:10.1002/1878-0261.12360

Cited by 29 publications

(38 citation statements)

References 29 publications

(125 reference statements)

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“…We investigated the prognosis significance of the upregulated and druggable genes. Excluding those genes with no clinical relevance, and those which have already been associated with PCa, such as Ctsb, Gpx2, Idh1, and Nos2 [60][61][62][63][64][65][66], we selected the antioxidant enzyme Srxn1 that had a strong correlation with patient outcome and has no previous related functional studies in PCa.…”

Section: Oxidative Stress Response Genes Are Deregulated Duringmentioning

confidence: 99%

Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer

Barquilha

Santos

Monção

et al. 2020

Oxidative Medicine and Cellular Longevity

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The incidence of prostate cancer (PCa) is increasing, and it is currently the second most frequent cause of death by cancer in men. Despite advancements in cancer therapies, new therapeutic approaches are still needed for treatment-refractory advanced metastatic PCa. Cross-species analysis presents a robust strategy for the discovery of new potential therapeutic targets. This strategy involves the integration of genomic data from genetically engineered mouse models (GEMMs) and human PCa datasets. Considering the role of antioxidant pathways in tumor initiation and progression, we searched oxidative stress-related genes for a potential therapeutic target for PCa. First, we analyzed RNA-sequencing data from Pb-Cre4; Ptenf/f mice and discovered an increase in sulfiredoxin (Srxn1) mRNA expression in high-grade prostatic intraepithelial neoplasia (PIN), well-differentiated adenocarcinoma (medium-stage tumors), and poor-differentiated adenocarcinoma (advanced-stage prostate tumors). The increase of SRXN1 protein expression was confirmed by immunohistochemistry in mouse prostate tumor paraffin samples. Analyses of human databases and prostate tissue microarrays demonstrated that SRXN1 is overexpressed in a subset of high-grade prostate tumors and correlates with aggressive PCa with worse prognosis and decreased survival. Analyses in vitro showed that SRXN1 expression is also higher in most PCa cell lines compared to normal cell lines. Furthermore, siRNA-mediated downregulation of SRXN1 led to decreased viability of PCa cells LNCaP. In conclusion, we identified the antioxidant enzyme SRXN1 as a potential therapeutic target for PCa. Our results suggest that the use of specific SRXN1 inhibitors may be an effective strategy for the adjuvant treatment of castration-resistant PCa with SRXN1 overexpression.

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Section: Oxidative Stress Response Genes Are Deregulated Duringmentioning

confidence: 99%

Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer

Barquilha

Santos

Monção

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Epidermal growth factor cytoplasmic domain (EGFcyt) was identi ed as an inducer of lysosomal cathepsin B expression in thyroid and glioma carcinoma cells [54]. Metastasis-associated protein (MTA1) inhibits cathepsin B expression in prostate cancer [55]. By mRNA sequencing and functional validation, CD147 was identi ed as a novel regulator of cathepsin B, which mediated CD147-faciliated collective invasion in HCC.…”

Section: Discussionmentioning

confidence: 99%

CD147 promotes collective invasion through cathepsin B in hepatocellular carcinoma

Wang

Chen

Wei

et al. 2020

Preprint

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Background Mounting evidence suggests that solid tumors display the features of collective invasion, however, the molecular mechanisms are far from clear. This study aims to verify the role and the underlying mechanisms of CD147 in collective invasion in hepatocellular carcinoma. Methods Immunostaining was used to analyze human hepatocellular carcinoma specimens and three-dimensional cultures. Three-dimensional invasion model was established to mimic in vivo invasion. RNA-sequencing was used to identify downstream effectors. Results Human hepatocellular carcinoma undergone collective invasion and CD147 was observed to be upregulated at the invasive front of tumor cell groups. CD147 was demonstrated to promote collective invasion using the modified three-dimensional invasion model, which recapitulated the main features of collective invasion. Through transcriptome analysis and enzyme activity assay, we found that CD147 enhanced cathepsin B expression and activation. Upregulated cathepsin B in hepatocellular carcinoma cells facilitated migration and invasion, which mediated CD147-induced invasive phenotype in hepatocellular carcinoma. In terms of mechanism, we found that CD147 promoted cathepsin B transcription by activating β-catenin signaling as a result of reduced GSK-3β expression. Furthermore, we found that elevated expression of CD147 as well as cathepsin B were correlated with poor prognosis in patients with hepatocellular carcinoma. Conclusions CD147 promotes hepatocellular carcinoma cells collective invasion via upregulating cathepsin B expression and targeting CD147 would be valuable for the development of novel therapeutic modalities against invasion and metastasis of cancer.

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“…Prostate cancer cells, DU145 and PC3M, were maintained in RPMI-1640 media containing 10% FBS in an incubator at 37 °C with 5% CO 2 as described previously [ 3 , 6 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 33 , 34 , 36 ]. Cells were authenticated using short tandem repeat profiling at Research Technology Support Facility, Michigan State University.…”

Section: Methodsmentioning

confidence: 99%

“…Colony formation assay was performed as described previously [ 33 ]. Briefly, cells (5 × 10 3 ) were seeded in a 35 mm cell culture dish for a 21-day observation time.…”

Section: Methodsmentioning

confidence: 99%

“…Our interest includes AR-independent pathways that play a role in the progression of PCa. One of these pathways is represented by an overexpression of metastasis-associated protein 1 (MTA1) and the subsequent activation of MTA1-mediated pro-oncogenic signaling associated with the progression of PCa to metastasis [ 3 , 11 , 12 , 13 , 16 , 32 , 33 , 34 , 35 , 36 ]. Clinical studies have demonstrated the correlation of high MTA1 expression in prostate tissues with aggressive clinicopathological characteristics of tumors, signifying MTA1 as a potential therapeutic target in PCa.…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Anticancer Properties of Table Grape Powder Extract (GPE) in Prostate Cancer

et al. 2018

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Although the link between diet and cancer is complex, epidemiological data confirm that diet is a risk factor for prostate cancer and indicate a reduced prostate cancer incidence associated with a diet rich in vegetables and fruits. Because of the known protective effect of grape seed extract (GSE) against prostate cancer, we evaluated the effects of grape powder extract (GPE) on cell viability, proliferation, and metastatic capability. Importantly, we explored the possible novel mechanism of GPE through metastasis-associated protein 1 (MTA1) downregulation in prostate cancer, since our previous studies indicated resveratrol (Res)- and pterostilbene (Pter)-induced MTA1-mediated anticancer activities in prostate cancer. We found that GPE inhibited the cell viability and growth of prostate cancer cells only at high 100 μg/mL concentrations. However, at low 1.5–15 μg/mL concentrations, GPE significantly reduced the colony formation and wound healing capabilities of both DU145 and PC3M cells. Moreover, we found that GPE inhibited MTA1 in a dose-dependent manner in these cells, albeit with considerably less potency than Res and Pter. These results indicate that stilbenes such as Res and Pter specifically and potently inhibit MTA1 and MTA1-associated proteins compared to GPE, which contains low concentrations of Res and mainly consists of other flavonoids and anthocyanidins. Our findings support continued interest in GPE as a chemopreventive and anti-cancer agent against prostate cancer but also emphasize the unique and specific properties of stilbenes on MTA1-mediated anticancer effects on prostate cancer.

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MTA1 drives malignant progression and bone metastasis in prostate cancer

Cited by 29 publications

References 29 publications

Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer

Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer

CD147 promotes collective invasion through cathepsin B in hepatocellular carcinoma

In Vitro Anticancer Properties of Table Grape Powder Extract (GPE) in Prostate Cancer

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