Phosphoglycerate Mutase 1 (PGAM1) Promotes Pancreatic Ductal Adenocarcinoma (PDAC) Metastasis by Acting as a Novel Downstream Target of the PI3K/Akt/mTOR Pathway

Liu, Xinlu; Tan, Xiaodong; Liu, Peng; Wu, Yunhao; Qian, Songying; Zhang, Xiaobo

doi:10.3727/096504018x15166223632406

Cited by 37 publications

(35 citation statements)

References 24 publications

(12 reference statements)

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“…Foregoing investigations have revealed PGAM1 overexpression in several cancers such as clear cell renal carcinoma (CCRC), glioma, oral squamous cell carcinoma (OSCC), breast cancer, human nonsmall lung cancer, pancreatic ductal adenocarcinoma, prostate cancer, colorectal cancer, hepatocellular carcinoma, and urothelial bladder cancer ( Table and Figure ).…”

Section: Overexpression Of Pgam1 In Various Cancersmentioning

confidence: 99%

“…Phosphatidylinositol‐4, 5‐bisphosphosphate 3 kinase (P13K) regulates the level of HIF‐1 α by its target protein kinase B (AKT). 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%

“…PGAM1 and hypoxia inducible factor both have mutual positive regulation as downstream targets of mTOR. Silencing of PGAM1 by siRNA leads to a significant decrease in proliferation of pancreatic cancer …”

Section: Genetic Inhibitors Of Pgam1mentioning

confidence: 99%

“…27 Thus, PGAM1 has potential ability to derive the metastasis in a metabolic independent way. 31 breast cancer, 32 human nonsmall lung cancer, 33 pancreatic ductal adenocarcinoma, 34 prostate cancer, 35 colorectal cancer, 36 hepatocellular carcinoma, 14 and urothelial bladder cancer 37 ( Table 2 and Figure 3). In the hypoxia tumor microenvironment, cancer cells are oxygen independent for energy production.…”

Section: Nonmetabolic Functions Of Pgam1mentioning

confidence: 99%

“…P13K phosphorylation activity regulates the AKT, and may have various downstream possessions such as mTOR and HIF-1 α. 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.…”

Section: Regulatory Network Of Pgam1mentioning

confidence: 99%

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

et al. 2019

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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.

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Section: Overexpression Of Pgam1 In Various Cancersmentioning

confidence: 99%

Section: Regulatory Network Of Pgam1mentioning

confidence: 99%

Section: Genetic Inhibitors Of Pgam1mentioning

confidence: 99%

Section: Nonmetabolic Functions Of Pgam1mentioning

confidence: 99%

Section: Regulatory Network Of Pgam1mentioning

confidence: 99%

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

et al. 2019

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

Liu

Wang

et al. 2022

Molecular Oncology

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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.

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Circ‐PGAM1 promotes malignant progression of epithelial ovarian cancer through regulation of the miR‐542‐3p/CDC5L/PEAK1 pathway

et al. 2020

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BackgroundEpithelial ovarian cancer (EOC) is the most common ovarian malignant cancer. Circular RNA is a type of endogenous noncoding RNA and is considered as a novel regulatory molecule in the development and progression of tumors. This study investigated the expression and functions of a circular RNA, circular‐phosphoglycerate mutase 1 (circ‐PGAM1), in EOC tissues and cells.MethodsThe expression of circ‐PGAM1 and miR‐542‐3p in EOC was analyzed using quantitative RT‐PCR. Immunohistochemistry and western blot were performed to confirm the localization and expression of cell division cycle 5‐like (CDC5L) and pseudopodium enriched atypical kinase 1 (PEAK1) in EOC tissues. Cell lines (CAOV3 and OVCAR3) overexpressing or silencingcirc‐PGAM1 and miR‐542‐3p were established to explore the functions of circ‐PGAM1 and miR‐542‐3p in ovarian cancer cells. Furthermore, dual‐luciferase reporter assay was performed to study the interactions between circ‐PGAM1 and miR‐542‐3p and between miR‐542‐3p and CDC5L. CCK‐8, transwell, and flow cytometry were used to study the effect of circ‐PGAM1 and miR‐542‐3p on cell biological behaviors including proliferation, migration, invasion, and apoptosis. The interaction between CDC5L and the PEAK1 gene promoter was confirmed using chromatin immunoprecipitation (ChIP).ResultsCirc‐PGAM1 was upregulated in EOC tissues, whereas linear PGAM1 was not deregulated in EOC tissues. Silencing of circ‐PAGM1 inhibited proliferation, migration, and invasion of ovarian cancer cells and promoted cell apoptosis. MiR‐542‐3p was downregulated in EOC tissues, and miR‐542‐3p overexpression inhibited malignant progression of ovarian cancer cells. Circ‐PGAM1 directly interacted with miR‐542‐3p, with mutual negative feedback between them. CDC5L was a direct target of miR‐542‐3p and played an oncogenic role in ovarian cancer cells. Furthermore, the CDC5L protein binds directly to the PEAK1 promoter to promote its transcription. PEAK1 overexpression activated ERK1/2 and JAK2 signaling pathways and promoted malignant biological behaviors of ovarian cancer cells. Circ‐PAGM1 silencing combined with miR‐542‐3p overexpression played the greatest anticancer role in vivo.ConclusionThe circ‐PGAM1/miR‐542‐3p/CDC5L/PEAK1 pathway played an important role in the progression of ovarian cancer and might be a novel therapeutic target for ovarian cancer.

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Phosphoglycerate Mutase 1 (PGAM1) Promotes Pancreatic Ductal Adenocarcinoma (PDAC) Metastasis by Acting as a Novel Downstream Target of the PI3K/Akt/mTOR Pathway

Cited by 37 publications

References 24 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

Circ‐PGAM1 promotes malignant progression of epithelial ovarian cancer through regulation of the miR‐542‐3p/CDC5L/PEAK1 pathway

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