MiR-1 Downregulation Cooperates with MACC1 in Promoting <i>MET</i> Overexpression in Human Colon Cancer

Migliore, Cristina; Martin, Valentina; Leoni, Vera P.; Restivo, Angelo; Atzori, Luigi; Petrelli, Annalisa; Isella, Claudio; Zorcolo, Luigi; Sarotto, Ivana; Casula, G.; Comoglio, Paolo M.; Columbano, Amedeo; Giordano, Silvia

doi:10.1158/1078-0432.ccr-11-1699

Cited by 110 publications

(70 citation statements)

References 54 publications

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“…The MET oncogene encodes a tyrosine kinase receptor that binds hepatocyte growth factor (HGF) and drives the malignant progression of several tumour types (Reid et al 2012). Experiments in CRC cells have confirmed the tumour-suppressive ability of miR-1, as enforced expression impairs cell scattering, migration, wound-healing and proliferation in response to HGF (Migliore et al 2012). Thus, activation of MET, due to a decrease in miR-1 is likely to be associated to cancer progression and to the acquisition of an invasive phenotype and metastatic dissemination (Migliore et al 2012, Reid et al 2012.…”

Section: Global Mirna Profiling Reveals a Signature Specific For Smalmentioning

confidence: 99%

“…Experiments in CRC cells have confirmed the tumour-suppressive ability of miR-1, as enforced expression impairs cell scattering, migration, wound-healing and proliferation in response to HGF (Migliore et al 2012). Thus, activation of MET, due to a decrease in miR-1 is likely to be associated to cancer progression and to the acquisition of an invasive phenotype and metastatic dissemination (Migliore et al 2012, Reid et al 2012. Interestingly, our bioinformatic analyses revealed HGF to also be targeted by miR-1 and we found HGF levels significantly increased in LN and liver metastases compared with primary SBNETs (Supplementary Fig.…”

Section: Global Mirna Profiling Reveals a Signature Specific For Smalmentioning

confidence: 99%

“…Deep sequencing has also found miR-1 levels to be reduced in colorectal cancers (CRCs) and a case of colorectal NET (Hamfjord et al 2012). miR-1 downregulation in human CRCs has been correlated with over-expression of the MET gene, especially in advanced stages of progression (Migliore et al 2012). The MET oncogene encodes a tyrosine kinase receptor that binds hepatocyte growth factor (HGF) and drives the malignant progression of several tumour types (Reid et al 2012).…”

Section: Global Mirna Profiling Reveals a Signature Specific For Smalmentioning

confidence: 99%

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MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

Miller¹,

Frampton²,

Malczewska³

et al. 2016

Endocrine-Related Cancer

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Novel molecular analytes are needed in small bowel neuroendocrine tumours (SBNETs) to better determine disease aggressiveness and predict treatment response. In this study, we aimed to profile the global miRNome of SBNETs, and identify microRNAs (miRNAs) involved in tumour progression for use as potential biomarkers. Two independent miRNA profiling experiments were performed (n = 90), including primary SBNETs (n = 28), adjacent normal small bowel (NSB; n = 14), matched lymph node (LN) metastases (n = 24), normal LNs (n = 7), normal liver (n = 2) and liver metastases (n = 15). We then evaluated potentially targeted genes by performing integrated computational analyses. We discovered 39 miRNAs significantly deregulated in SBNETs compared with adjacent NSB. The most upregulated (miR-204-5p, miR-7-5p and miR-375) were confirmed by qRT-PCR. Two miRNAs (miR-1 and miR-143-3p) were significantly downregulated in LN and liver metastases compared with primary tumours. Furthermore, we identified upregulated gene targets for miR-1 and miR-143-3p in an existing SBNET dataset, which could contribute to disease progression, and show that these miRNAs directly regulate FOSB and NUAK2 oncogenes. Our study represents the largest global miRNA profiling of SBNETs using matched primary tumour and metastatic samples. We revealed novel miRNAs deregulated during SBNET disease progression, and important miRNA-mRNA interactions. These miRNAs have the potential to act as biomarkers for patient stratification and may also be able to guide treatment decisions. Further experiments to define molecular mechanisms and validate these miRNAs in larger tissue cohorts and in biofluids are now warranted.

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Section: Global Mirna Profiling Reveals a Signature Specific For Smalmentioning

confidence: 99%

Section: Global Mirna Profiling Reveals a Signature Specific For Smalmentioning

confidence: 99%

Section: Global Mirna Profiling Reveals a Signature Specific For Smalmentioning

confidence: 99%

See 1 more Smart Citation

MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

Miller¹,

Frampton²,

Malczewska³

et al. 2016

Endocrine-Related Cancer

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“…Clinical data show that MET overexpression, in the absence of gene amplifi cation, is the most frequent cause of constitutive MET activation in human tumors and often correlates with poor prognosis. Overexpression can be caused by several factors, such as hypoxia ( 19 ), activation of upstream oncogenes ( 20,21 ), inactivation of tumor suppressor genes ( 22 ), or loss of miRNAs ( 23,24 ). MET gene amplifi cation, which drives increased expression and constitutive receptor activation, has been described in selected histotypes such as gastroesophageal, colorectal, endometrial, and lung carcinomas, glioblastomas, and medulloblastomas (reviewed in ref.…”

Section: Met/hgf and Cancermentioning

confidence: 99%

Cell-Autonomous and Non–Cell-Autonomous Mechanisms of HGF/MET–Driven Resistance to Targeted Therapies: From Basic Research to a Clinical Perspective

Corso

Giordano

2013

Cancer Discovery

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Targeted therapies have opened new perspectives in clinical oncology. However, clinicians have observed a lack of response in a relevant percentage of patients and frequent relapse in patients who initially respond. Therefore, a compelling challenge is to identify mechanisms underlying resistance and strategies to circumvent these hurdles. A growing body of evidence indicates that MET, the tyrosine kinase receptor for hepatocyte growth factor (HGF), is frequently implicated in resistance to targeted therapies. In this review, we highlight cell-autonomous and non-cell-autonomous mechanisms through which MET drives resistance, and we discuss some unsolved issues related to the selection of patients who could benefi t from combined therapies. Signifi cance:Resistance is, at present, the major limitation to the effi cacy of targeted therapies. Inappropriate MET activation is very frequently implicated in the onset of primary and secondary resistance to these therapies. Deciphering the role of the HGF/MET axis in resistance to different drugs could guide the design of new clinical trials based on combinatorial therapies, and it might help to overcome, or possibly prevent, the onset of resistance. Cancer Discov; 3(9);

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“…Metastasis-associated in colon cancer-1 (MACC1) has been reported to promote tumor proliferation and invasion mediated via hepatocyte growth factor (HGF)/ mesenchymal-epithelial transition factor (c-Met) signaling in colorectal cancer (Stein et al, 2009;Galimi et al, 2011;Migliore et al, 2012). Recently, a clinical study showed that aberrant overexpression of MACC1 may indicate poor prognosis of ovarian cancer patients for early recurrence and distance metastasis (Zhang et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Aberrant Expression of Pim-3 Promotes Proliferation and Migration of Ovarian Cancer Cells

Zhuang¹,

Zhao²,

Hei³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Pim kinase-3(Pim-3), a member of serine/threonine protein kinases, has been implicated in multiple human cancers and involved in Myc-induced tumorigenesis. However, little is known regarding its expression and biological function in human ovarian cancer. In this study we showed that the clinical significance and biological functions of Pim-3 in ovarian cancer and found that higher Pim-3 mRNA level are detected in ovarian cancer tissues than those in normal ovarian tissues. There are significant correlations between higher Pim-3 expression levels with the FIGO stage, histopathological subtypes, and distant metastasis in ovarian cancer patients. Lentivirus-mediated gene overexpression of Pim-3 significantly promotes the proliferation and migration of SKOV3 cell lines. Furthermore, MACC1 and Pim-3 expression were significantly correlated in human ovarian cancer cells, and overexpression of Pim-3 in ovary cancer cells increased MACC1 mRNA and protein expression. The data indicate that Pim-3 acts as a putative oncogene in ovary cancer and could be a viable diagnostic and therapeutic target for ovarian cancer.

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MiR-1 Downregulation Cooperates with MACC1 in Promoting MET Overexpression in Human Colon Cancer

Cited by 110 publications

References 54 publications

MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

Cell-Autonomous and Non–Cell-Autonomous Mechanisms of HGF/MET–Driven Resistance to Targeted Therapies: From Basic Research to a Clinical Perspective

Aberrant Expression of Pim-3 Promotes Proliferation and Migration of Ovarian Cancer Cells

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