The potential of carboxypeptidase M as a therapeutic target in cancer

Denis, Catherine J.; Lambeir, Anne‐Marie

doi:10.1517/14728222.2012.741122

Cited by 27 publications

(18 citation statements)

References 87 publications

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“…CPs are zinc-dependent enzymes that have been reported to be correlated with a range of physiological and biological processes, such as oncogenesis. For example, carboxypeptidase E (CPE) is suggested to be dysregulated and participate in the metastases of serval human malignancies, 13,24 highlighting the vital role of certain CPs in the regulation of malignant biological properties. To date, some CPs have been recognized as potential therapeutic and diagnostic biomarkers.…”

Section: Discussionmentioning

confidence: 99%

“…10,11 Although not all CPs exhibit active peptidase activity, members of the M14 family have various physiological functions on account of their substrate specificity, tissue distribution, and cellular and subcellular localization. 12,13 Carboxypeptidase X (CPX), M14 family member 2 (CPXM2) is a member of the M14 family and has been shown to be associated with several developmental disorders by affecting the cell-cell interactions. [14][15][16][17] To date, the impact of CPXM2 on HCC tumorigenesis has not been further explored.…”

Section: Introductionmentioning

confidence: 99%

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<p>Expression of Carboxypeptidase X M14 Family Member 2 Accelerates the Progression of Hepatocellular Carcinoma via Regulation of the gp130/JAK2/Stat1 Pathway</p>

Ye¹,

An²,

Wang³

et al. 2020

CMAR

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Background: Carboxypeptidase X, M14 family member 2 (CPXM2) has been reported to be involved with several human malignancies. However, the impact of CPXM2 on human hepatocellular carcinoma (HCC) tumorigenesis has not been studied. Materials and Methods: Using immunohistochemistry, the detailed CPXM2 expression patterns were examined in HCC cell lines and tissues. Additionally, a hepatic stellate cell line overexpressing CPXM2 and an HCC CPXM2-knockdown cell line were established by lipofection of an expression plasmid or short hairpin RNA, respectively. The transfection efficiencies were confirmed by reverse transcription-quantitative PCR, Western blotting and immunofluorescence. Moreover, Western blotting was conducted to determine the phosphorylation levels of the tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 3 (Stat1) pathway. Furthermore, gp130-specific hairpin RNA was used to knockdown gp130 expression in hepatic stellate cells overexpressing CPXM2. The malignant phenotype of cultured HCC cells was assessed by a Cell Counting Kit-8 (CCK8) assay, plate cloning assay, Matrigel invasion assay and wound-healing assay in vitro. Results: It was demonstrated that CPXM2 was upregulated in HCC, and its upregulation predicted a poor prognosis. Besides, the upregulation of CPXM2 markedly enhanced the metastatic potential of HCC via the gp130/JAK2/Stat1 signaling pathway in vitro. Conclusion: In summary, this evidence suggests a positive role for CPXM2 in HCC progression via modulation of the gp130/JAK2/Stat1 signaling pathway in HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

<p>Expression of Carboxypeptidase X M14 Family Member 2 Accelerates the Progression of Hepatocellular Carcinoma via Regulation of the gp130/JAK2/Stat1 Pathway</p>

Ye¹,

An²,

Wang³

et al. 2020

CMAR

View full text Add to dashboard Cite

show abstract

“…Previous study has shown elevated expression of CPA3 in asthma (43) and anaphylactic shock (44); however, few studies have investigated the role of CPA3 in cancers. CPM is also an arginine/lysine CP and exerts important roles in angiogenesis, proliferation, and apoptosis through modulating chemokines or kinins in cancer cells (45). Notably, recent study reports that CPM/Src-FAK pathway is involved in the cell migration and invasion in colon cancer (46).…”

Section: Discussionmentioning

confidence: 99%

The identification of a potential prognostic model of colon cancer using integrated bioinformatics analysis

Fang

Xie

et al. 2020

Preprint

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Abstract Background This study aimed to construct prognostic model by screening prognostic gene signature of colon cancer. Methods The gene expression profile data of colon cancer were obtained from The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) and differently expressed genes (DEGs) between tumor and control samples were identified. Prognosis-associated genes were then identified and used for the construction of prognostic model. The independent factors that associated with the prognosis of colon in the TCGA cohort was identified. Results Totally, 1153 consistent DEGs were screened out between tumor and normal tissues in the TCGA cohort, GSE44861 and GSE44076 datasets. Among these genes, 12 DEGs were related to the prognosis of colon cancer and were used for constructing the prognostic model. This model presented a high predictive power for the prognosis of colon cancer both in the training dataset and in the validation datasets (AUC > 0.8). Statistical analysis showed that age, pathological T, tumor recurrence, and model status were the independent factors for prognosis of patients with colon cancer in TCGA. Conclusions The 12-gene signature prognostic model had a high predictive power for colon cancer prognosis.

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“…CPM was less reported, and only one literature revealed that it was the target of miR-146a which promoted cell migration and invasion in CRC via CPM/src-FAK pathway ( 34 ). It was suggested that CPM has the potential to be a therapeutic target in cancer ( 35 ), but its function still need further discovery. SHMT2 participated in the cellular one-carbon metabolism, and has been implicated as a critical component for tumor survival.…”

Section: Discussionmentioning

confidence: 99%

A five‑gene based risk score with high prognostic value in colorectal cancer

Pan

Zhang

et al. 2017

Oncol Lett

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Colorectal cancer (CRC) is one of the most frequently occurring malignancies worldwide. The outcomes of patients with similar clinical symptoms or at similar pathological stages remain unpredictable. This inherent clinical diversity is most likely due to the genetic heterogeneity. The present study aimed to create a predicting tool to evaluate patient survival based on genetic profile. Firstly, three Gene Expression Omnibus (GEO) datasets (GSE9348, GSE44076 and GSE44861) were utilized to identify and validate differentially expressed genes (DEGs) in CRC. The GSE14333 dataset containing survival information was then introduced in order to screen and verify prognosis-associated genes. Of the 66 DEGs, the present study screened out 46 biomarkers closely associated to patient overall survival. By Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, it was demonstrated that these genes participated in multiple biological processes which were highly associated with cancer proliferation, drug-resistance and metastasis, thus further affecting patient survival. The five most important genes, MET proto-oncogene, receptor tyrosine kinase, carboxypeptidase M, serine hydroxymethyltransferase 2, guanylate cyclase activator 2B and sodium voltage-gated channel a subunit 9 were selected by a random survival forests algorithm, and were further made up to a linear risk score formula by multivariable cox regression. Finally, the present study tested and verified this risk score within three independent GEO datasets (GSE14333, GSE17536 and GSE29621), and observed that patients with a high risk score had a lower overall survival (P<0.05). Furthermore, this risk score was the most significant compared with other predicting factors including age and American Joint Committee on Cancer stage, in the model, and was able to predict patient survival independently and directly. The findings suggest that this survival associated DEGs-based risk score is a powerful and accurate prognostic tool and is promisingly implemented in a clinical setting.

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The potential of carboxypeptidase M as a therapeutic target in cancer

Cited by 27 publications

References 87 publications

<p>Expression of Carboxypeptidase X M14 Family Member 2 Accelerates the Progression of Hepatocellular Carcinoma via Regulation of the gp130/JAK2/Stat1 Pathway</p>

<p>Expression of Carboxypeptidase X M14 Family Member 2 Accelerates the Progression of Hepatocellular Carcinoma via Regulation of the gp130/JAK2/Stat1 Pathway</p>

The identification of a potential prognostic model of colon cancer using integrated bioinformatics analysis

A five‑gene based risk score with high prognostic value in colorectal cancer

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