Phosphoglyceric acid mutase-1 contributes to oncogenic mTOR-mediated tumor growth and confers non-small cell lung cancer patients with poor prognosis

Sun, Qian; Li, Shuzhan; Wang, Yanan; Peng, Haiyong; Zhang, Xiying; Zheng, Yu; Li, Chunjia; Li, Li; Chen, Rongrong; Chen, Xinxin; Bai, Wenjing; Jiang, Xiaoming; Liu, Liang; Wei, Feng; Wang, Boshi; Zhang, Yu; Li, Hui; Ren, Xiubao; Zhang, Hongbing

doi:10.1038/s41418-017-0034-y

Cited by 62 publications

(53 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Downregulation of PGAM1 is an auspicious approach that targets both glycolysis as well as other two biosynthesis pathways for the cure of cancer . Silencing of PGAM1 expression diminishes the prostate cancer (PCa) cell proliferation, invasion potential, and induces apoptosis through downregulation of MMP‐2 and MMP‐9 proteins .…”

Section: Pgam1 As Potential Therapeutic Drug Targetmentioning

confidence: 99%

“…P13K phosphorylation activity regulates the AKT, and may have various downstream possessions such as mTOR and HIF‐1 α . Alterations and over activation in RTK/PI3K/AKT/mTOR pathway identifies in 74% squamous cell lung cancer samples (RTK 26% as well as PI3K 47%) …”

Section: Regulatory Network Of Pgam1mentioning

confidence: 99%

“…Higher expression of PGAM1 in NSCLC tissues was found to be associated with distant/lymph node metastasis and clinical stage. Thus, PGAM1 was found to have novel prognostic relevance conferring poor prognosis to the patients . PGAM1 overexpression was analyzed in 122 tissue samples from OSCC patients by immunohistochemistry.…”

Section: Pgam1 As Diagnostic and Prognostic Biomarkermentioning

confidence: 99%

“…Downregulation of PGAM1 is an auspicious approach that targets both glycolysis as well as other two biosynthesis pathways for the cure of cancer. 38 Silencing of PGAM1 expression diminishes the prostate cancer (PCa) cell proliferation, invasion potential, and induces apoptosis through downregulation of MMP-2 and MMP-9 proteins. 35 Deficiency of PGAM1 by PGAM1-004A, which is the small molecule inhibitor, escalates the intracellular 3-PG level and reduces 2-PG level ultimately suppressing the Pancreatic Ductal Adenocarcinoma (PDAC).…”

Section: Pgam1 As Potential Therapeutic Drug Targetmentioning

confidence: 99%

“…34 Alterations and over activation in RTK/PI3K/AKT/mTOR pathway identifies in 74% squamous cell lung cancer samples (RTK 26% as well as PI3K 47%). 38,40 In many human cancers, tyrosine signaling cascade is significantly upregulated. PGAM1 is activated upon phosphorylation at histidine 11 (H11), in the presence of cofactor 2, 3-BPG, by shifting the C3 phosphate to H11.…”

Section: Regulatory Network Of Pgam1mentioning

confidence: 99%

See 4 more Smart Citations

Phosphoglycerate mutase 1 in cancer: A promising target for diagnosis and therapy

et al. 2019

View full text Add to dashboard Cite

Altered enzymatic machineries are a substantial biochemical characteristic of tumor cell metabolism that switch metabolic profile from oxidative phosphorylation to amplified glycolysis as well as increased lactate production under hypoxia conditions. Reprogrammed metabolic profile is an emerging hallmark of cancer. Overexpression of several glycolytic enzymes and glucose transporters has been reported in 24 different types of cancers that represent approximately 70% of all the cancer cases around the globe. Thus, targeting glycolytic enzymes could serve as tempting avenue for drug design against cancer. Phosphoglycerate mutase 1 (PGAM1) is an important glycolytic enzyme that catalyzes the conversion of 3‐phosphoglycerate to 2‐phosphoglycerate. Recent investigations have revealed the overexpression of PGAM1 in several human cancers that is linked with tumor growth, survival, and invasion. The aim of this review is to update scientific research network with cancer‐specific role of PGAM1 to elucidate its capability as bonafide therapeutic target for cancer therapy. Moreover, we have also summarized the reported genetic and pharmacological inhibitors of PGAM1. This study suggests that further investigations on PGAM1 should focus on the exploration of molecular mechanisms of PGAM1 overexpression in development of cancer, assessment of biosafety profiles of known inhibitors of PGAM1, and utilization of PGAM1 inhibitors in combinatorial therapies. These future studies will surely support the unbiased strategies for the development of novel PGAM1 inhibitors for cancer therapies.

show abstract

Section: Pgam1 As Potential Therapeutic Drug Targetmentioning

confidence: 99%

Section: Regulatory Network Of Pgam1mentioning

confidence: 99%

Section: Pgam1 As Diagnostic and Prognostic Biomarkermentioning

confidence: 99%

Section: Pgam1 As Potential Therapeutic Drug Targetmentioning

confidence: 99%

Section: Regulatory Network Of Pgam1mentioning

confidence: 99%

See 3 more Smart Citations

Phosphoglycerate mutase 1 in cancer: A promising target for diagnosis and therapy

et al. 2019

View full text Add to dashboard Cite

show abstract

PGAM1 regulation of ASS1 contributes to the progression of breast cancer through the cAMP/AMPK/CEBPB pathway

Liu

Wang

et al. 2022

Molecular Oncology

Self Cite

View full text Add to dashboard Cite

Phosphoglycerate mutase 1 (PGAM1) is a crucial glycolytic enzyme, and its expression status has been confirmed to be associated with tumor progression and metastasis. However, the precise role and other biological functions of PGAM1 remain unclear. Here, we report that PGAM1 expression is upregulated and related to poor prognosis in patients with breast cancer (BC). Functional experiments showed that knockdown of PGAM1 could suppress the proliferation, invasion, migration, and epithelial–mesenchymal transition of BC cells. Through RNA sequencing, we found that argininosuccinate synthase 1 (ASS1) expression was markedly upregulated in BC cells following PGAM1 knockdown, and it is required to suppress the malignant biological behavior of BC cells. Importantly, we demonstrated that PGAM1 negatively regulates ASS1 expression through the cAMP/AMPK/CEBPB axis. In vivo experiments further validated that PGAM1 promoted tumor growth in BC by altering ASS1 expression. Finally, immunohistochemical analysis showed that downregulated ASS1 levels were associated with PGAM1 expression and poor prognosis in patients with BC. Our study provides new insight into the regulatory mechanism of PGAM1‐mediated BC progression that might shed new light on potential targets and combination therapeutic strategies for BC treatment.

show abstract

The regulatory roles and clinical significance of glycolysis in tumor

Qiao,

Hu,

Wang

2024

Cancer Communications

View full text Add to dashboard Cite

Metabolic reprogramming has been demonstrated to have a significant impact on the biological behaviors of tumor cells, among which glycolysis is an important form. Recent research has revealed that the heightened glycolysis levels, the abnormal expression of glycolytic enzymes, and the accumulation of glycolytic products could regulate the growth, proliferation, invasion, and metastasis of tumor cells and provide a favorable microenvironment for tumor development and progression. Based on the distinctive glycolytic characteristics of tumor cells, novel imaging tests have been developed to evaluate tumor proliferation and metastasis. In addition, glycolytic enzymes have been found to serve as promising biomarkers in tumor, which could provide assistance in the early diagnosis and prognostic assessment of tumor patients. Numerous glycolytic enzymes have been identified as potential therapeutic targets for tumor treatment, and various small molecule inhibitors targeting glycolytic enzymes have been developed to inhibit tumor development and some of them are already applied in the clinic. In this review, we systematically summarized recent advances of the regulatory roles of glycolysis in tumor progression and highlighted the potential clinical significance of glycolytic enzymes and products as novel biomarkers and therapeutic targets in tumor treatment.

show abstract

Phosphoglyceric acid mutase-1 contributes to oncogenic mTOR-mediated tumor growth and confers non-small cell lung cancer patients with poor prognosis

Cited by 62 publications

References 52 publications

Phosphoglycerate mutase 1 in cancer: A promising target for diagnosis and therapy

Phosphoglycerate mutase 1 in cancer: A promising target for diagnosis and therapy

PGAM1 regulation of ASS1 contributes to the progression of breast cancer through the cAMP/AMPK/CEBPB pathway

The regulatory roles and clinical significance of glycolysis in tumor

Contact Info

Product

Resources

About