Function Of KLK10 In Liver Metastasis Of Pancreatic Ductal Adenocarcinoma And TPR In Progression Of Hepatocellular Carcinoma

An important phase of cancer progression is metastasis to other organs.Sixteen common cancers metastasize to the liver in their process.Pancreatic ductal adenocarcinoma is a malignant tumor characterized by invasion and metastasis.The 5-year survival rate of patients with pancreatic cancer is less than 5%.KLK10 is a member of the kallikrein family,a secreted serine protease.Studies have shown that members of the KLK family can promote cancer to metastases.We screened KLK10,a specificilly and highly expressed molecule in PDAC by database analysis.Renji tissue chip and spontaneous PDAC animal model confirmed that KLK10 is up-regulated as the disease progresses and highly expressed in liver metastasis cancer tissue.We found knockdown KLK10 inhibited metastasis of PDAC,in vitro and in vivo.Knockdown of KLK10 downregulated p-FAK?p-Src and p-ERK.Hepatocellular Carcinoma is among the world's top three lethality cancers,and also the most common malignant tumor in our country.Difficulty of early diagnosis,high recurrence and metastasis rate give rise to high mortality of liver cancer.TPR,Translocated Promoter Region,also known as Nuclear Basket Protein.TPR is an important composition of nuclear complex,it involved in the process of material out nuclear shippment.Also,TPR has multiple phosphorylation sites and serves as a scaffold involved in the phosphorylation of other proteins.In the present study,we found that TPR was highly expressed in HCC and correlated with prognosis.The experiment found that silencing TPR could inhibit the proliferation of HCC cells,leading to abnormal cell division.We found that TPR expression was regulated by Hippo pathway YAP and TEAD through chromatin immunoprecipitation and luciferase reporter.In addition,we also found that TPR interacted with RacGAP1 through protein coimmunoprecipitation.In the anaphase of mitosis,both of them co-localized on the cytoplasmic contraction ring.Our study shows that in hepatocellular carcinoma,the expression of TPR is regulated by YAP and TEAD,and TPR interacts with RacGAP1 to affect the proliferation of hepatoma cells.