Dataset Information

Calcium-binding protein S100P is a new target gene of MACC1, drives colorectal cancer metastasis and serves as a prognostic biomarker.

ABSTRACT:

Background

The metastasis inducing gene MACC1 is a prognostic and predictive biomarker for metastasis in several cancers. Its mechanism of inducing metastasis includes the transcriptional control of other cancer-related target genes. Here, we investigate the interplay with the metastasis driver S100P in CRC progression.

Methods

MACC1-dependent S100P expression was analysed by qRT-PCR. The binding of MACC1 to the S100P promoter was determined by ChIP. Alterations in cell proliferation and motility were determined by functional in vitro assays. In vivo metastasis after intrasplenic transplantation was assessed by bioluminescence imaging and evaluation of tumour growth and liver metastasis. The prognostic value of S100P was determined in CRC patients by ROC-based Kaplan-Meier analyses.

Results

Expression of S100P and MACC1 correlated positively in CRC cells and colorectal tumours. MACC1 was found binding to the S100P promoter and induces its expression. The overexpression of S100P increased proliferation, migration and invasion in vitro and significantly induced liver metastasis in vivo. S100P expression was significantly elevated in metachronously metastasising CRC and was associated with shorter metastasis-free survival.

Conclusions

We identified S100P as a transcriptional target gene of MACC1. Expression of S100P increases the metastatic potential of CRC cells in vitro and in vivo, and serves as a prognostic biomarker for metastasis-free survival of CRC patients, emphasising novel therapeutic interventions targeting S100P.

SUBMITTER: Schmid F

PROVIDER: S-EPMC9381557 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Calcium-binding protein S100P is a new target gene of MACC1, drives colorectal cancer metastasis and serves as a prognostic biomarker.

Schmid Felicitas F Dahlmann Mathias M Röhrich Hanna H Kobelt Dennis D Hoffmann Jens J Burock Susen S Walther Wolfgang W Stein Ulrike U

British journal of cancer 20220521 4

<h4>Background</h4>The metastasis inducing gene MACC1 is a prognostic and predictive biomarker for metastasis in several cancers. Its mechanism of inducing metastasis includes the transcriptional control of other cancer-related target genes. Here, we investigate the interplay with the metastasis driver S100P in CRC progression.<h4>Methods</h4>MACC1-dependent S100P expression was analysed by qRT-PCR. The binding of MACC1 to the S100P promoter was determined by ChIP. Alterations in cell proliferat ...[more]

PMID: 35597866

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Project description:BackgroundTo research the correlation between the prognosis of patients suffering from lung adenocarcinoma (LUAD) and methyltransferase like 7B (METTL7B) expression.MethodsThe Cancer Genome Atlas (TCGA) database was utilized to verify METTL7B expression, and The Human Protein Atlas database was utilized to verify METTL7B expression at the tissue level. The relationship between METTL7B and LUAD prognostic data was then analyzed using the KM-plotter database. The correlation between METTL7B expression and immune cells was demonstrated through the TIMER database. For exploring the possible mechanism of action, gene set enrichment analysis (GSEA) was performed. Finally, the role of METTL7B in the adverse biological events of LUAD was further explored by in vitro experiments such as proliferation and invasion assays.ResultsAs per the TCGA database, METTL7B expression was increased in cancerous tissues compared with paracancerous tissues, and it was mostly located in the cytoplasm. Patients suffering from LUAD who had low METTL7B expression had a relatively better overall survival (OS) and disease-specific survival (DSS) according to the Kaplan-Meier-plotter (KM-plotter) database. METTL7B expression was significantly associated with immune cell infiltration in LUAD patients, as shown by correlation analysis. GSEA revealed that METTL7B may affect the physiological events of LUAD by playing a part in cell cycle regulation. In vitro cytological experiments demonstrated that METTL7B can markedly affect the metastasis of LUAD cells.ConclusionsThe reduction of METTL7B expression can prolong OS and DSS in LUAD patients. It may be utilized as a novel predictive biomarker of LUAD, and may be associated with immune infiltration of LUAD. Interfering with METTL7B expression can significantly cause inhibition of LUAD by modulating the ability of cells to proliferate and migrate. These results point to a possible target for developing anti-cancer therapies against LUAD.

Project description:BackgroundMetastasis is the most frequent cause of treatment failure and death in colorectal cancer. Early detection of tumors and metastases is crucial for improving treatment strategies and patient outcome. Development of reliable biomarkers and simple tests routinely applicable in the clinic for detection, prognostication, and therapy monitoring is of special interest. We recently identified the novel gene Metastasis-Associated in Colon Cancer 1 (MACC1), a key regulator of the HGF/Met-pathway. MACC1 is a strong prognostic biomarker for colon cancer metastasis and allows identification of high-risk subjects in early stages, when determined in patients' primary tumors. To overcome the limitation of a restricted number of molecular analyses in tumor tissue, the establishment of a non-invasive blood test for early identification of high-risk cancer patients, for monitoring disease course and therapy response is strongly needed.Methodology/principal findingsFor the first time, we describe a non-invasive assay for quantification of circulating MACC1 transcripts in blood of more than 300 colorectal cancer patients. MACC1 transcript levels are increased in all disease stages of the cancer patients compared to tumor-free volunteers. Highest MACC1 levels were determined in individuals with metastases (all P<0.05). Importantly, high MACC1 levels correlate with unfavorable survival (P<.0001). Combining MACC1 with circulating transcripts of the metastasis gene S100A4, a transcriptional target of the Wnt/?-catenin-pathway, improves survival prediction for newly diagnosed cancer patients.Conclusion/significanceThis blood-based assay for circulating MACC1 transcripts, which can be quantitated on a routine basis, is clinically applicable for diagnosis, prognosis, and therapeutic monitoring of cancer patients. Here we demonstrate the diagnostic and prognostic value of circulating MACC1 transcripts in patient plasma for metastasis and survival. Since MACC1 represents a promising target for anti-metastatic therapies, circulating MACC1 transcripts may prove to be an ideal read-out for monitoring therapeutic response of future interventions targeting MACC1-induced metastasis in cancer patients.

Dataset Information

Calcium-binding protein S100P is a new target gene of MACC1, drives colorectal cancer metastasis and serves as a prognostic biomarker.

Background

Methods

Results

Conclusions

Publications

Calcium-binding protein S100P is a new target gene of MACC1, drives colorectal cancer metastasis and serves as a prognostic biomarker.

Similar Datasets

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