The potential therapeutic and prognostic impacts of the c‐MET/HGF signaling pathway in colorectal cancer

Parizadeh, Seyed Mostafa; Fazilat‐Panah, Danial; Hassanian, Seyed Mahdi; Shahidsales, Soodabeh; Ferns, Gordon A.

doi:10.1002/iub.2063

Cited by 48 publications

(43 citation statements)

References 68 publications

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“…Activation of HGF/MET can initiate downstream signalling pathways that drive malignant progression in many types of tumors. MET is considered an essential factor for early invasion and metastasis of CRC and can be regarded as an important prognostic indicator [17,18]. In the present study, we found that CREB5 promotes CRC invasion and metastasis by increasing MET expression to activate HGF-MET signalling.…”

Section: Introductionsupporting

confidence: 60%

“…Immunohistochemistry (IHC) staining was performed as previously described using CREB5 antibody (Abcam, USA, ab168928) [20]. The degree of IHC staining was reviewed and scored independently by two observers based on both the proportion of positively stained tumor cells and the intensity of staining [18,19]. The proportion of tumor cells was scored as follows: 0 (no positive tumor cells), 1 (< 10% positive tumor cells), 2 (10-50% positive tumor cells), and 3 (> 50% positive tumor cells).…”

Section: Immunohistochemistrymentioning

confidence: 99%

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CREB5 promotes invasiveness and metastasis in colorectal cancer by directly activating MET

Wang

Qiu

Liu

et al. 2020

J Exp Clin Cancer Res

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Background: cAMP responsive element binding protein 5 (CREB5) is a transcriptional activator in eukaryotic cells that can regulate gene expression. Previously, we found that CREB5 was involved in the occurrence and development of colorectal cancer (CRC) using bioinformatics analysis. However, the biological roles and underlying regulatory mechanism of CREB5 in CRC remain unclear. Methods: Real-time PCR, western blotting, and immunohistochemistry were used to examine CREB5 expression. In vitro experiments including migration assay, wound-healing assay, chicken chorioallantoic membrane assay, and human umbilical vein endothelial cells tube formation assay were used to investigate the effects of CREB5 on CRC cell migration and tumor angiogenesis ability. Additionally, an orthotopic implantation assay was performed in nude mice to confirm the effects of CREB5 in vivo. Furthermore, gene set enrichment analysis was performed to explore the potential mechanism of CREB5 in CRC. Results: We found that CREB5 expression was highly upregulated in CRC. CREB5 overexpression was positively correlated with advanced WHO stages and TNM stages and shorter survival in CRC patients. Moreover, CREB5 overexpression promoted while CREB5 silencing reduced the invasiveness and metastatic capacity of CRC cells both in vitro and in vivo. Furthermore, CREB5 directly interacted with the MET promoter and activated the hepatocyte growth factor-MET signalling pathway. Importantly, inhibition of MET reduced the invasion and metastasis of CREB5-overexpressing CRC cells, suggesting that CREB5 promotes metastasis mainly through activation of MET signalling. Conclusion: Our study demonstrates a crucial role for CREB5 in CRC metastasis by directly upregulating MET expression. CREB5 may be both a potential prognostic marker and a therapeutic target to effectively overcome metastasis in CRC.

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Section: Introductionsupporting

confidence: 60%

Section: Immunohistochemistrymentioning

confidence: 99%

CREB5 promotes invasiveness and metastasis in colorectal cancer by directly activating MET

Wang

Qiu

Liu

et al. 2020

J Exp Clin Cancer Res

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“…Dysregulation of the MET signaling pathway occurs in a wide range of human cancers, including breast, colorectal, lung, pancreatic, hepatic, and ovarian cancers [39][40][41][42]. Inhibition of MET signaling has emerged as a promising approach for cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circBFAR promotes the progression of pancreatic ductal adenocarcinoma via the miR-34b-5p/MET/Akt axis

Guo

Zhou

et al. 2020

Mol Cancer

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Background: Accumulating evidence suggests that circular RNAs (circRNAs) are important participants in cancer progression. However, the biological processes and underlying mechanisms of circRNAs in pancreatic ductal adenocarcinoma (PDAC) are unclear. Method: CircRNAs were verified by Sanger sequencing. Colony formation, 5-Ethynyl-2′-deoxyuridine (EdU), and Transwell assays were performed to investigate the effect of circBFAR on the proliferation, invasion, and migration of PDAC cells in vitro. RNA pull-down assays were conducted to verify the binding of circBFAR with microRNA miR-34b-5p.

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“…Recently, according to changes in dietary patterns and physical activity, CRC has dramatically increased in China [2]. Despite the advanced surgery technologies and medicine treatments have been applicated in CRC treatment, the survival rate of patients with CRC still remains unsatisfactory [3][4][5][6][7]. Hence, the mechanisms underlying CRC progression is urgent calling for new breakthrough.…”

Section: Introductionmentioning

confidence: 99%

Hsa_circRNA_000166 facilitated cell growth and limited apoptosis through targeting miR-326 / LASP1 axis in colorectal cancer

Hao

Zhang²

2020

Preprint

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Background: Circular RNAs(circRNAs) belong to non-coding RNAs and widely expressed in a variety of cell species, including cancers. However, the function and mechanism of circRNAs in colorectal cancer (CRC) has not been well investigated. Methods: Microarray data of CRC from Gene Expression Omnibus (GEO) database was used to obtain DEGs. QRT-PCR and western blot assay were performed to determine the mRNA and protein levels of multiple genes, respectively. Cell growth and apoptosis assay were conducted to measure CRC cell proliferation and apoptosis, respectively. Luciferase assay was utilized to confirm the direct interaction between hsa_circRNA_000166 and miR-326. Results: We downloaded and analyzed the circRNA expression profile of CRC from the GEO database and identified 181 differentially expressed circRNAs between 10 pairs of CRC and adjacent normal tissues. Interestingly, we observed that the expression of hsa_circRNA_000166 was the top increased among these circRNAs. Then, we confirmed an upregulation of hsa_circRNA_000166 in CRC tissues and cell lines and observed that higher expression of hsa_circRNA_000166 was associated with poor 5-year survival rate of patients with CRC. Cell growth and apoptosis assay revealed that hsa_circRNA_000166 regulated the cell growth and apoptosis in CRC cell lines. Furthermore, we identified that hsa_circRNA_000166 targeted miR-326/LASP1 pathway using bioinformatic analysis and luciferase reporter assay. Finally, overexpression of miR-326 could sufficiently rescued the aberrant cell growth and apoptosis in CRC cell lines. Conclusion: Taken together, our results indicated that downregulation of hsa_circRNA_000166 inhibited the cell growth and facilitated apoptosis during CRC development by sponging miR-326 / LASP1 pathway.

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The potential therapeutic and prognostic impacts of the c‐MET/HGF signaling pathway in colorectal cancer

Cited by 48 publications

References 68 publications

CREB5 promotes invasiveness and metastasis in colorectal cancer by directly activating MET

CREB5 promotes invasiveness and metastasis in colorectal cancer by directly activating MET

Circular RNA circBFAR promotes the progression of pancreatic ductal adenocarcinoma via the miR-34b-5p/MET/Akt axis

Hsa_circRNA_000166 facilitated cell growth and limited apoptosis through targeting miR-326 / LASP1 axis in colorectal cancer

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