Somatic Ephrin Receptor Mutations Are Associated with Metastasis in Primary Colorectal Cancer

Mathot, Lucy; Kundu, Snehangshu; Ljungström, Viktor; Svedlund, Jessica; Moens, Lotte; Adlerteg, Tom; Falk-Sörqvist, Elin; Rendo, Verónica; Bellomo, Claudia; Mayrhofer, Markus; Cortina, Carme; Sundström, Magnus; Micke, Patrick; Botling, Johan; Isaksson, Anders; Moustakas, Aristidis; Batlle, Eduard; Birgisson, Helgi; Glimelius, Bengt; Nilsson, Mats; Sjöblom, Tobias

doi:10.1158/0008-5472.can-16-1921

Cited by 31 publications

(54 citation statements)

References 55 publications

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“…1 CRC is often diagnosed at an advanced stage, is accompanied by metastasis, which is negatively correlated with patient survival, and CRC remains incurable. [2][3][4] Therefore, the discovery of new diagnostic and prognostic markers and a better understanding of the molecular mechanisms of colorectal tumorigenesis and metastasis are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

SSRP1 promotes colorectal cancer progression and is negatively regulated by miR‐28‐5p

Guo

et al. 2019

J Cellular Molecular Medi

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In this study, microarray data analysis, real‐time quantitative PCR and immunohistochemistry were used to detect the expression levels of SSRP1 in colorectal cancer (CRC) tissue and in corresponding normal tissue. The association between structure‐specific recognition protein 1 (SSRP1) expression and patient prognosis was examined by Kaplan‐Meier analysis. SSRP1 was knocked down and overexpressed in CRC cell lines, and its effects on proliferation, cell cycling, migration, invasion, cellular energy metabolism, apoptosis, chemotherapeutic drug sensitivity and cell phenotype‐related molecules were assessed. The growth of xenograft tumours in nude mice was also assessed. MiRNAs that potentially targeted SSRP1 were determined by bioinformatic analysis, Western blotting and luciferase reporter assays. We showed that SSRP1 mRNA levels were significantly increased in CRC tissue. We also confirmed that this upregulation was related to the terminal tumour stage in CRC patients, and high expression levels of SSRP1 predicted shorter disease‐free survival and faster relapse. We also found that SSRP1 modulated proliferation, metastasis, cellular energy metabolism and the epithelial‐mesenchymal transition in CRC. Furthermore, SSRP1 induced apoptosis and SSRP1 knockdown augmented the sensitivity of CRC cells to 5‐fluorouracil and cisplatin. Moreover, we explored the molecular mechanisms accounting for the dysregulation of SSRP1 in CRC and identified microRNA‐28‐5p (miR‐28‐5p) as a direct upstream regulator of SSRP1. We concluded that SSRP1 promotes CRC progression and is negatively regulated by miR‐28‐5p.

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Section: Introductionmentioning

confidence: 99%

SSRP1 promotes colorectal cancer progression and is negatively regulated by miR‐28‐5p

Guo

et al. 2019

J Cellular Molecular Medi

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“…Significant molecular alterations affecting PI3K-Akt, Wnt, Hippo, mTOR, PDGF (platelet-derived growth factor), and FGF (fibroblast growth factor) signaling pathways are also described [ 23 , 25 , 59 ]. Included among the mutated genes in these pathways are APC , ARID1A , BMPR1A , CHEK2 , DVL1 , EPHB1 , FBXW7 , KDR , MAP2K1 , PDGFRA , PTEN , RB1 , SMARCA4 , SMARCB1 , HRAS , NRAS , and WRN [ 23 , 24 , 59 , 70 , 76 , 77 ], whose genetic alterations have also been found in lung adenocarcinomas [ 78 , 79 , 80 ], colorectal [ 81 , 82 , 83 , 84 ], and breast cancers [ 85 ]. Moreover, oncogenic mutations in ABL1 , EP300 , PIK3CA , PIK3C2B , PTPN11 , and SETDB1 genes [ 23 , 24 , 25 , 59 , 62 ], and novel gains in regions encompassing RHEB , KDM5A , AXIN2 , RICTOR , TRIO , and DVL1 genes were identified [ 24 , 65 ].…”

Section: Genomics Of Malignant Pleural Mesotheliomamentioning

confidence: 99%

Genomics and Functional Genomics of Malignant Pleural Mesothelioma

Çakıroğlu

Şentürk

2020

IJMS

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Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the mesothelial cells lining the pleural surface of the chest wall and lung. The etiology of MPM is strongly associated with prior exposure to asbestos fibers, and the median survival rate of the diagnosed patients is approximately one year. Despite the latest advancements in surgical techniques and systemic therapies, currently available treatment modalities of MPM fail to provide long-term survival. The increasing incidence of MPM highlights the need for finding effective treatments. Targeted therapies offer personalized treatments in many cancers. However, targeted therapy in MPM is not recommended by clinical guidelines mainly because of poor target definition. A better understanding of the molecular and cellular mechanisms and the predictors of poor clinical outcomes of MPM is required to identify novel targets and develop precise and effective treatments. Recent advances in the genomics and functional genomics fields have provided groundbreaking insights into the genomic and molecular profiles of MPM and enabled the functional characterization of the genetic alterations. This review provides a comprehensive overview of the relevant literature and highlights the potential of state-of-the-art genomics and functional genomics research to facilitate the development of novel diagnostics and therapeutic modalities in MPM.

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“…The therapeutic applications of Eph receptors include monoclonal antibody targeting, soluble Eph fusion protein targeting, small molecule Eph kinase inhibitors, dendritic-cell based vaccines, and siRNAs [ 10 , 229 – 233 ]. However, these therapeutic modalities suffer from deficiencies such as varying effectiveness of antibodies, deleterious side effects, redundancy of functions, receptor-independent activation of signaling pathways, variable effects of Eph receptors in T-cell lineage development, and epigenetic regulation of Eph expression [ 61 , 97 , 229 – 241 ].…”

Section: Discussionmentioning

confidence: 99%

Differential Expression Patterns of Eph Receptors and Ephrin Ligands in Human Cancers

Kou

Kandpal

2018

BioMed Research International

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Eph receptors constitute the largest family of receptor tyrosine kinases, which are activated by ephrin ligands that either are anchored to the membrane or contain a transmembrane domain. These molecules play important roles in the development of multicellular organisms, and the physiological functions of these receptor-ligand pairs have been extensively documented in axon guidance, neuronal development, vascular patterning, and inflammation during tissue injury. The recognition that aberrant regulation and expression of these molecules lead to alterations in proliferative, migratory, and invasive potential of a variety of human cancers has made them potential targets for cancer therapeutics. We present here the involvement of Eph receptors and ephrin ligands in lung carcinoma, breast carcinoma, prostate carcinoma, colorectal carcinoma, glioblastoma, and medulloblastoma. The aberrations in their abundances are described in the context of multiple signaling pathways, and differential expression is suggested as the mechanism underlying tumorigenesis.

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Somatic Ephrin Receptor Mutations Are Associated with Metastasis in Primary Colorectal Cancer

Cited by 31 publications

References 55 publications

SSRP1 promotes colorectal cancer progression and is negatively regulated by miR‐28‐5p

SSRP1 promotes colorectal cancer progression and is negatively regulated by miR‐28‐5p

Genomics and Functional Genomics of Malignant Pleural Mesothelioma

Differential Expression Patterns of Eph Receptors and Ephrin Ligands in Human Cancers

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