| BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of malignant tumors. Most of the patients have metastasis and lose the opportunity to resection when diagnosed. Therefore, searching the markers of metastasis and prognosis of PDAC is necessary. Integrin pathway is an important signal pathway which involved in metastasis and invasion of tumors. In the previous study, we used CIPHER, database and bibliographic retrieval to predict the markers, and the result showed that Talin-1, β1 and β3 integrin perhaps involved in prognosis of PDAC patients.Talin-1 is in cytoplasm and consists of head and rod, which can affect the function of integrin protein on cell membrane. Talin-1 can activate integrin and promote the focal adhesion between cells and extracellular matrix. Meanwhile, the rod of Talin-1 can recruit cytoskeleton proteins and influence cell movement. Additionally, Talin-1 can affect many cell signal pathways by regulating FAK, SFK and some other cytokines. Talin-1 is associated with many cancers, including prostatic cancer, breast cancer, liver cancer, squamous carcinoma and ovarian carcinoma. It can influence survival and metastasis of cancer cells. Furthermore, its effect on the outcome of cancer might be tissue-type specific. However, the correlation between Talin-1 expression and clinicopathological characteristics of PDAC and its role in pancreatic cancer have not been reported.We will use tissue microarray to investigate the relationship between Talin-1 expression and clinicopathological characteristics of PDAC. At the same time, we will study the correlations between Talin-1 expression and the functions of cancer cell in vitro.Objective1. Investigated the expression of Talin-1 in pancreatic cancer and correlation between Talin-1 expression and clinicopathological characteristics of PDAC and its role in prognosis of PDAC patients.2. Investigated the expression of Talin-1 in pancreatic cancer cells; explored the effect of Talin-1 on proliferation, apoptosis, adhesion, invasion and migration of pancreatic cancer cells.3. Investigated the related mechanism of Talin-1 influencing PDAC.Methods1. The expression of Talin-1,β1 and βintegrin was evaluated using tissue microarray-based immunohistochemistry on tumor tissues and adjacent nontumor tissues from patients with pancreatic ductal adenocarcinoma (PDAC). The associations between expression levels of the three markers, clinicopathological factors, and overall survival were evaluated.2. The expression of Talin-1 in different PDAC cell lines was evaluated by real-time PCR and western blotting. Talin-1 was silenced using transient transfection of siRNA. Cell proliferation was detected using the CCK-8 and EdU kit; apoptosis analysis was detected by flow cytometry; adhesion analysis was performed on fibronectin coated plates; cell migration and invasion activity assays were detected by transwell.3. Using co-transfection to inhibit the expression of Talin-1 and β3 integrin simultaneously. And analysing the proliferation, adhesion, migration and invasion of co-transfected cancer cells.Results1. Comparing with the adjacent normal tissues, the expression of Talin-1 was lower in PDAC and was related to the focus location of tumor, and when β1 integrin expression was high, it was associated with N stage significantly. When β1 or β3 integrin expression was high, Talin-1 expression was related to the overall survival of patients.2. Talin-1 could significantly promote proliferation and adhesion of PANC-1, and inhibit migration and invasion simultaneously.3. When inhibiting the expression of β3 integrin, Talin-1 can promote proliferation and adhesion of PANC-1, as the results when β3 integrin expression was normal. However, when β3 integrin expression decreased, Talin-1 could not influence migration, indeed, it promoted invasion of cancer cells.ConclusionWhen β1 or β3 integrin expression was high, Talin-1 was related to the prognosis of PDAC patients significantly. Talin-1 could promote proliferation and adhesion of cancer cells, and inhibit migration and invasion by cooperating with β3 integrin. |
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