Knockdown of Slit2 promotes growth and motility in gastric cancer cells via activation of AKT/β-catenin

Shi, Ruihan; Yang, Zhen; Liu, Weiyan; Liu, Bingya; Xu, Zu-De; Zhang, Ziping

doi:10.3892/or.2013.2887

Cited by 30 publications

(30 citation statements)

References 30 publications

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“…Furthermore, frequent and diverse somatic aberrations in SLIT/ROBO signalling pathway have been reported in B20% of pancreatic adenocarcinomas 38 . Knockdown of SLIT2 promotes growth and motility in GC cells via activation of AKT/CTNNB1 (b-catenin), suggesting tumour suppressor role 39 . On the basis of these findings, the Ephrins and SLIT/ROBO signalling pathways may be involved in the development of GC and could be a therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

Genomic landscape and genetic heterogeneity in gastric adenocarcinoma revealed by whole-genome sequencing

et al. 2014

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Gastric cancer (GC) is the second most common cause of cancer-related deaths. It is known to be a heterogeneous disease with several molecular and histological subtypes. Here we perform whole-genome sequencing of 49 GCs with diffuse (N ¼ 31) and intestinal (N ¼ 18) histological subtypes and identify three mutational signatures, impacting TpT, CpG and TpCp[A/T] nucleotides. The diffuse-type GCs show significantly lower clonality and smaller numbers of somatic and structural variants compared with intestinal subtype. We further divide the diffuse subtype into one with infrequent genetic changes/low clonality and another with relatively higher clonality and mutations impacting TpT dinucleotide. Notably, we discover frequent and exclusive mutations in Ephrins and SLIT/ROBO signalling pathway genes. Overall, this study delivers new insights into the mutational heterogeneity underlying distinct histologic subtypes of GC that could have important implications for future research in the diagnosis and treatment of GC.

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Section: Discussionmentioning

confidence: 99%

Genomic landscape and genetic heterogeneity in gastric adenocarcinoma revealed by whole-genome sequencing

et al. 2014

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“…SLIT2 regulates the β-catenin/TCF and PI3K/AKT signaling pathways and enhances cell-cell adhesion in breast cancer (10). Knockdown of SLIT2 promotes gastric cancer cell proliferation and migration via activation of AKT/β-catenin signaling (11). SLIT2 and SLIT3 are frequently methylated and downregulated in various cancers such as breast (12), colorectal (13), cervical (14), and lung (12), but their methylation status in gastric cancer has not been unequivocally defined.…”

Section: Introductionmentioning

confidence: 99%

Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes

Kim

Baek

et al. 2016

International Journal of Oncology

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Abstract. SLIT has been suggested as a key regulator of cancer development and a promising therapeutic target for cancer treatment. Herein, we analyzed expression and methylation of SLIT1/SLIT2/SLIT3 in 11 gastric cancer cell lines, 96 paired gastric tumors and adjacent normal gastric tissues, and 250 gastric cancers provided by The Cancer Genome Atlas. Methylation of SLIT1/SLIT2/SLIT3 was found both in early gastric cancers, and in advanced gastric cancers. Even normal gastric tissue showed increased methylation of SLIT1 and SLIT3 that correlated with patient age. Furthermore, epigenetic inactivation of SLIT occurred in a gastric cancer subtype-dependent manner. SLIT2 and SLIT3 expression was reduced in Epstein-Barr virus-positive and microsatellite instability subtypes, but increased in the genomically stable subtype. Expression of miR-218 correlated negatively with methylation of SLIT2 or SLIT3. These findings suggest that a molecular subtype-specific therapeutic strategy is needed for targeting SLITs and miR-218 in treatment of gastric cancer.

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“…Our previous study identified Slit2 as a diagnosis and prognosis marker in gastric cancer. Mechanistically, it participates in gastric cancer oncogenesis and metastasis through regulating the AKT/β-catenin pathway (15,16).To the best of our knowledge, the expression pattern of Slit2 and its correlation with clinicpathological parameters of PTC has not been previously reported. In the present study, we examined Slit2 expression in transcriptional and protein level, and then analyzed the correlation between Slit2 expression and the clinicopatholocical characteristics of PTC.…”

mentioning

confidence: 87%

“…Thus, the role of Slit2 in cancer is distinct depending on the cancer type. Our previous studies (15,16) in gastric cancer indicated that Slit2 is a tumor suppressor. The expression of Slit2 was higher in gastric patients with less advanced clinicopathological features.…”

Section: Discussionmentioning

confidence: 99%

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Expression, clinical significance and mechanism of Slit2 in papillary thyroid cancer

Shi

Liao

et al. 2016

International Journal of Oncology

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Abstract. Thyroid cancer is a common endocrine malignancy. The last decade has seen exciting progress in understanding thyroid cancer molecular pathogenesis. Several major signaling pathways and related molecular derangements have been elucidated, which represent novel diagnostic and prognostic molecular markers for thyroid cancer. Based on the molecular biology of thyroid cancer, a series of therapeutic targets have been developed, which provide unprecedented opportunities. Thus, histological characterization of subgroups of patients and the correct molecular characterization of patients are thought to be key aspects for future clinical management of these patients. In the present study, we identified Slit2 as a prognostic marker for thyroid cancer oncogenesis and recurrence. Mechanistically, Slit2 regulated Warburg effect in thyroid cancer cells through regulation of HIF1α and HIF1α transcriptional activity. Taken together, our present data uncovered Slit2 as a novel predictive marker for thyroid cancer. The mechanism study indicated that Slit2 regulated the Warburg effect. Additional study on the function of Slit2 in thyroid cancer is required to provide new insights into the potential mechanisms of oncogenesis and recurrence potential of thyroid cancer. IntroductionThyroid carcinoma is an endocrine-related malignancy. Among thyroid carcinoma, papillary thyroid cancer (PTC) is the most common type and account for 80-90% of total thyroid carcinoma cases (1,2). Although the clinical prognosis for the majority of cases is satisfactory, 14% demonstrate early recurrence and some present severe invasion, multiple lymph node metastasis and distant metastasis (3-5). Currently the progress in identification of biological markers that are useful for the diagnosis and prognosis analysis of PTC is slow (6). Thus, the correct molecular characterization and identification of patients with thyroid cancer is thought to be a key aspect for future study.Slit refers to a family of related genes which encode a corresponding set of secreted proteins, also collectively referred to as Slit (7). The classical function of Slit in proteins is to act as midline repellents, preventing the crossing of longitudinal axons through the midline of the central nervous system of most bilaterian animal species. It also prevents the recrossing of commissural axons (8). Its canonical receptor is ROBO, and Slit/ROBO signaling is important in pioneer axon guidance (9-11). In recent years, the role of Slit family proteins in cancer has received much attention due to their role in controlling cell migration, abnormalities or absence in the expression in Slit proteins are associated with a variety of cancers (12-14). Our previous study identified Slit2 as a diagnosis and prognosis marker in gastric cancer. Mechanistically, it participates in gastric cancer oncogenesis and metastasis through regulating the AKT/β-catenin pathway (15,16).To the best of our knowledge, the expression pattern of Slit2 and its correlation with clinicpathological parameters of...

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Knockdown of Slit2 promotes growth and motility in gastric cancer cells via activation of AKT/β-catenin

Cited by 30 publications

References 30 publications

Genomic landscape and genetic heterogeneity in gastric adenocarcinoma revealed by whole-genome sequencing

Genomic landscape and genetic heterogeneity in gastric adenocarcinoma revealed by whole-genome sequencing

Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes

Expression, clinical significance and mechanism of Slit2 in papillary thyroid cancer

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