Enhanced expression of IMPDH2 promotes metastasis and advanced tumor progression in patients with prostate cancer

Zhou, Lizhi; Xia, Dan; Zhu, Jian; Chen, Yun-Xia; Chen, G.; Mo, Rujun; Zeng, Yue; Dai, Qi-Shan; He, Hui‐Chan; Liang, Yingying; Jiang, Fan; Zhong, Weide

doi:10.1007/s12094-014-1167-9

Cited by 25 publications

(24 citation statements)

References 21 publications

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“…Increased expression of IMPDH2 is associated with progression of kidney and bladder cancer [35]. Promotion of metastasis and advanced tumor progression in patients with prostate cancer is also associated with increased IMPDH2 expression [36]. Likewise, gene expression of PDI ( PDIA3 and PDIA6 ) was shown to be a marker for aggressiveness in primary ductal breast cancer [37].…”

Section: Discussionmentioning

confidence: 99%

Withaferin A inhibits in vivo growth of breast cancer cells accelerated by Notch2 knockdown

Kim

Hahm

Arlotti

et al. 2016

Breast Cancer Res Treat

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Purpose The present study offers novel insights into the molecular circuitry of accelerated in vivo tumor growth by Notch2 knockdown in triple-negative breast cancer (TNBC) cells. Therapeutic vulnerability of Notch2-altered growth to a small molecule (withaferin A; WA) is also demonstrated. Methods MDA-MB-231 and SUM159 cells were used for the xenograft studies. A variety of technologies were deployed to elucidate the mechanisms underlying tumor growth augmentation by Notch2 knockdown and its reversal by WA, including Fluorescence Molecular Tomography for measurement of tumor angiogenesis in live mice, Seahorse Flux analyzer for ex vivo measurement of tumor metabolism, proteomics, and Luminex-based cytokine profiling. Results Stable knockdown of Notch2 resulted in accelerated in vivo tumor growth in both cells reflected by tumor volume and/or latency. For example, the wet tumor weight from mice bearing Notch2 knockdown MDA-MB-231 cells was about 7.1-fold higher compared with control (P < 0.0001). Accelerated tumor growth by Notch2 knockdown was highly sensitive to inhibition by a promising steroidal lactone (WA) derived from a medicinal plant. Molecular underpinnings for tumor growth intensification by Notch2 knockdown included compensatory increase in Notch1 activation, increased cellular proliferation and/or angiogenesis, and increased plasma or tumor levels of growth stimulatory cytokines. WA administration reversed many of these effects providing explanation for its remarkable anti-cancer efficacy. Conclusions Notch2 functions as a tumor growth suppressor in TNBC and WA offers a novel therapeutic strategy for restoring this function.

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Section: Discussionmentioning

confidence: 99%

Withaferin A inhibits in vivo growth of breast cancer cells accelerated by Notch2 knockdown

Kim

Hahm

Arlotti

et al. 2016

Breast Cancer Res Treat

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“…IMPDH2 is frequently overexpressed in different forms of leukemia [161], colorectal [162], prostate [18], bladder, and kidney cancers [163]. Moreover, there are several evidences that its expression is associated with highly invasive, metastatic cancers [18, 163] resistant to cisplatin and MTX [164, 165].…”

Section: Other Inhibitors Of Metabolismmentioning

confidence: 99%

“…Moreover, there are several evidences that its expression is associated with highly invasive, metastatic cancers [18, 163] resistant to cisplatin and MTX [164, 165]. …”

Section: Other Inhibitors Of Metabolismmentioning

confidence: 99%

“…Notably, the growing body of evidence suggests that these metabolic pathways should be viewed as a complex network [8, 9, 11, 12]. Moreover, up-regulation of these pathways as well as specific oncogenic features of a number of functionally related enzymes of one-carbon metabolism, including phosphoglycerate dehydrogenase PHGDH [13], phosphoserine aminotransferase PSAT1 [14], phosphoserine phosphatase PSPH [15], serine hydroxymethyltransferase SHMT2 [16], glycine dehydrogenase GLDC [17], inosine-5′-monophosphate dehydrogenase IMPDH2 [18]- became also known.…”

Section: Introductionmentioning

confidence: 99%

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One-carbon metabolism and nucleotide biosynthesis as attractive targets for anticancer therapy

et al. 2017

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Cancer-related metabolism has recently emerged as one of the "hallmarks of cancer". It has several important features, including altered metabolism of glucose and glutamine. Importantly, altered cancer metabolism connects different biochemical pathways into the one fine-tuned metabolic network, which stimulates high proliferation rates and plasticity to malignant cells. Among the keystones of cancer metabolism are one-carbon metabolism and nucleotide biosynthesis, which provide building blocks to anabolic reactions. Accordingly, the importance of these metabolic pathways for anticancer therapy has well been documented by more than fifty years of clinical use of specific metabolic inhibitors -methotrexate and nucleotides analogs. In this review we discuss one-carbon metabolism and nucleotide biosynthesis as common and specific features of many, if not all, tumors. The key enzymes involved in these pathways also represent promising anti-cancer therapeutic targets. We review different aspects of these metabolic pathways including their biochemistry, compartmentalization and expression of the key enzymes and their regulation at different levels. We also discuss the effects of known inhibitors of these pathways as well as the recent data on other enzymes of the same pathways as perspective pharmacological targets.

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“…suggested that IMPDH2 could be used as a promising candidate for the stratification of osteosarcoma patients into low- and high-risk groups 16 . Recently, the protein expression level of IMPDH2 was found to be significantly upregulated in prostate, kidney and bladder cancers and could be a potential biomarker for these diseases 2, 17 . However, to the best of our knowledge, the expression status of IMPDH2 and its clinical significance in NPC remain unknown.…”

Section: Introductionmentioning

confidence: 99%

High expression of IMPDH2 is associated with aggressive features and poor prognosis of primary nasopharyngeal carcinoma

Zheng

Gao

et al. 2017

Sci Rep

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Inosine monophosphate dehydrogenase type II (IMPDH2) has been shown to play critical roles in the development and progression of several human cancers. However, little is known about IMPDH2 expression and its clinical significance in nasopharyngeal carcinoma (NPC). Western blotting, qRT-PCR and immunohistochemistry were employed to evaluate IMPDH2 expression in NPC cell lines and tissues. In our study, elevated expression of IMPDH2 was observed at both the protein and mRNA levels in NPC cell lines than in NPEC2 Bmi-1. IMPDH2 protein expression was markedly higher in NPC tissues than in adjacent non-tumorous tissues. Moreover, IMPDH2 expression in NPC correlated with several clinicopathological parameters, including T classification (P = 0.023), TNM stage (P = 0.020), distant metastasis (P = 0.001) and death (P = 0.002). Further Cox regression analysis suggested that IMPDH2 expression was an independent prognostic factor for overall survival (P = 0.001) and disease-free survival (P < 0.001). In addition, stratified survival analysis showed that high expression of IMPDH2 could be a prognostic factor for NPC patients with TNM stage I/II (OS: P = 0.012; DMFS: P = 0.007), TNM stage III/IV (OS: P = 0.028; DMFS: P = 0.020). Our study demonstrates IMPDH2 may be served as an independent prognostic biomarker for NPC patients, in which high IMPDH expression suggests poor prognosis of NPC patients.

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Enhanced expression of IMPDH2 promotes metastasis and advanced tumor progression in patients with prostate cancer

Abstract: These findings suggest for the first time that the enhanced expression of IMPDH2 may promote the tumor metastasis and the advanced tumor progression in patients with PCa.

Cited by 25 publications

References 21 publications

Withaferin A inhibits in vivo growth of breast cancer cells accelerated by Notch2 knockdown

Withaferin A inhibits in vivo growth of breast cancer cells accelerated by Notch2 knockdown

One-carbon metabolism and nucleotide biosynthesis as attractive targets for anticancer therapy

High expression of IMPDH2 is associated with aggressive features and poor prognosis of primary nasopharyngeal carcinoma

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