Search

Pancreatic ductal adenocarcinoma (PDAC) is a fatalmalignant cancer with extremely poor prognosis and high mortality. Genome wide studies show that Slit/Robo signaling pathway takes a major effect in the oncogenesis and progression of pancreatic cancer. However, the function and mechanism of ROBO2 in the development of PDAC remains unclear. In present study, we use Western blot and real-time polymerase chain reaction (RT-PCR) to detect the expression of ROBO2 in pancreatic cell lines. Cell proliferation,Transwellmigration and invasion were conducted inAsPC-1, MIA PaCa-2 and PANC-1cell lines. RNA sequencing, bioinformatics analysisand Western blot were used to explore its mechanism and potential target molecules. The expression of ROBO2 in 95 tumor tissues was detected by immunohistochemistry. ROBO2 expression was downregulated in PDAC cell lines and tissue samples. A high expression of ROBO2 was associated with better prognosis. Upregulation of ROBO2 inhibited PDAC cell proliferation, migration, and invasion. However, we found theoppositeresults in the ROBO2 downregulation group. In addition, the function of ROBO2 on cell proliferation was further affirmed by the animal model. Finally, the results of RNA sequencing indicated that ROBO2 partly promoted the antitumor activity by inhibiting ECM1 in PDAC. Our work suggests that ROBO2 inhibits tumor progression in PDAC and may serve as a predictive biomarker and therapeutic target in PDAC. [ABSTRACT FROM AUTHOR]

As a Rac1 guanine nucleotide exchange factor, T‐cell lymphoma invasion and metastasis 2 (TIAM2) has been reported to be correlated with malignant phenotypes in several cancers, but its prognostic significance and function in pancreatic ductal adenocarcinoma (PDAC) was not investigated. The expression patterns of TIAM2 and patient survival were analyzed in a large cohort of 303 patients with radical surgical resection of PDAC, using immunohistochemical staining in tissue microarrays. Data mining was applied to evaluate TIAM2 expression and patient survival at the mRNA level. The function of TIAM2 in proliferation, motility and invasion of pancreactic cancer (PC) cells was also investigated. TIAM2 expression was significantly increased in PDAC compared with para-tumor tissues (p <.0001). The expression of TIAM2 was associated with histopathological grade (p =.008), tumor location (p =.013), and pathological T stage (p =.029). For survival, patients with high TIAM2 expression had significantly poor prognosis in some subgroups. In addition, multivariate analyses showed that the combination of TIAM2 and the pathological N stage largely enhanced the prognostic efficiency, and was found to be as an independent prognostic indicator in patients with PDAC. Data mining elucidated that TIAM2 mRNA expression level was increased in tumor tissues and correlated with patient survival. Furthermore, high TIAM2 expression was common in PC cells. Downregulation of TIAM2 suppressed cell proliferation, migration and invasion in PC. High expression of TIAM2 might be a meaningful prognostic factor for PDAC patients, and TIAM2 participates in tumor progression in PDAC. [ABSTRACT FROM AUTHOR]