Slit2 expression and its correlation with subcellular localization of β-catenin in gastric cancer

Shi, Ruihan; Liu, Weiyan; Liu, Bing-ya; Xu, Zu-De; Chen, Liping; Zhang, Ziping

doi:10.3892/or.2013.2662

Cited by 14 publications

(17 citation statements)

References 20 publications

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“…5-7 The Slit-Robo signalling pathway plays important roles not only in neuronal guidance but also during cell migration of a wide range of cell types. 17,18 In contrast, two other reports suggested that Robo1 might promote tumorigenesis. 16 However, the precise function of the Slit-Robo pathway in the development of GC remains ill-defined.…”

Section: Introductionmentioning

confidence: 89%

Reduced USP33 expression in gastric cancer decreases inhibitory effects of Slit2‐Robo1 signalling on cell migration and EMT

Xia

Wang

et al. 2019

Cell Proliferation

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Objectives: Gastric cancer (GC) is one of the most common cancers in the world, causing a large number of deaths every year. The Slit-Robo signalling pathway, initially discovered for its critical role in neuronal guidance, has recently been shown to modulate tumour invasion and metastasis in several human cancers. However, the role of Slit-Robo signalling and the molecular mechanisms underlying its role in the pathogenesis of gastric cancer remains to be elucidated. Materials and methods:Slit2, Robo1 and USP33 expressions were analysed in datasets obtained from the Oncomine database and measured in human gastric cancer specimens. The function of Slit2-Robo1-USP33 signalling on gastric cancer cells migration and epithelial-mesenchymal transition (EMT) was studied both in vitro and in vivo. The mechanism of the interaction between Robo1 and USP33 was explored by co-IP and ubiquitination protein analysis. Results:The mRNA and protein levels of Slit2 and Robo1 are lower in GC tissues relative to those in adjacent healthy tissues. Importantly, Slit2 inhibits GC cell migration and suppresses EMT process in a Robo-dependent manner. The inhibitory function of Slit2-Robo1 is mediated by ubiquitin-specific protease 33 (USP33) via deubiquitinating and stabilizing Robo1. USP33 expression is decreased in GC tissues, and reduced USP33 level is correlated with poor patient survival. S U PP O RTI N G I N FO R M ATI O NAdditional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Xia Y, Wang L, Xu Z, et al. Reduced USP33 expression in gastric cancer decreases inhibitory effects of Slit2-Robo1 signalling on cell migration and EMT.

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Section: Introductionmentioning

confidence: 89%

Reduced USP33 expression in gastric cancer decreases inhibitory effects of Slit2‐Robo1 signalling on cell migration and EMT

Xia

Wang

et al. 2019

Cell Proliferation

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“…Knockdown of Slit2 activates β-catenin signaling through AKT. Our previous study revealed a correlation between loss of Slit2 expression and nuclear β-catenin in gastric cancer tissues (23). AKT, on the other hand, is one of the major kinases that phosphorylated and inactivated GSK3β and subsequently released and activated β-catenin signaling.…”

Section: Knockdown Of Slit2 Activates Akt-mediated Survival Signalingmentioning

confidence: 97%

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

et al. 2013

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We previously showed that Slit2 was highly expressed in gastric cancer tissues that exhibit less advanced clinicopathological features, suggesting a tumor suppressor role for Slit2. In the present study, we investigated the effects of Slit2 knockdown on gastric cancer cells. Slit2-specific shRNAs were used to generate Slit2-knockdown SGC-7901 gastric cancer cells. Cell proliferation assay, Annexin V/PI double staining and cell cycle analysis were used to investigate the role of Slit2 knockdown in cell growth. Wound-healing and in vitro migration/invasion assays were performed. Subcutaneous tumor formation and peritoneal spreading in nude mice were employed to examine the in vivo effects of Slit2 knockdown. Cell signaling changes induced by Slit2 knockdown were analyzed by immunoblotting. Slit2 knockdown increased gastric cancer cell growth in monolayer and soft agar/Matrigel 3D culture. Slit2 knockdown inhibited apoptosis but did not alter cell cycle progression. Slit2-knockdown cells formed larger tumors and produced more peritoneal metastatic nodules in nude mice. Slit2 knockdown increased AKT phosphorylation, activated anti-apoptotic signaling, suppressed GSK3β activity and induced β-catenin activation. Blocking the effects of PI3K/AKT using pharmacological inhibitors abolished the ability of Slit2 knockdown to induce apoptosis resistance and cell migration/invasion. These results indicate that Slit2 knockdown promotes gastric cancer growth and metastasis through activation of the AKT/β‑catenin-mediated signaling pathway.

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“…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: 98%

“…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.…”

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confidence: 90%

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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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Slit2 expression and its correlation with subcellular localization of β-catenin in gastric cancer

Cited by 14 publications

References 20 publications

Reduced USP33 expression in gastric cancer decreases inhibitory effects of Slit2‐Robo1 signalling on cell migration and EMT

Reduced USP33 expression in gastric cancer decreases inhibitory effects of Slit2‐Robo1 signalling on cell migration and EMT

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

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

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