| Research background and purpose:With the development of society and the change of surrounding natural environment,tumor has become one of the most dangerous diseases in the world.Esophageal carcinoma is one of the common digestive tract tumors.In recent years,it has become a malignant tumor with high morbidity and mortality in China and globally.Esophageal cancer by pathology type is mainly divided into:esophageal squamous cell carcinoma and esophageal adenocarcinoma,two different pathologic classification on the epidemiological characteristics and regional distribution there are larger differences,squamous carcinoma are mainly distributed in some developing countries.In China,the incidence of esophageal cancer is the highest in the world,of which more than 90%of the pathological types are esophageal squamous cell carcinoma(esophageal squamous cell carcinoma).Esophageal cancer has the characteristics of high morbidity and high invasiveness.It has ranked the 3rd in all kinds of tumors in mainland China,and the mortality rate is 4th.The symptoms of early esophageal squamous cell carcinoma are usually light and difficult to detect,so the prognosis of esophageal cancer is poor when most patients are diagnosed as esophageal cancer.A large number of scholars and experts have been engaged in research on the mechanism of esophageal squamous carcinoma,early screening diagnosis and treatment,etc.,and has obtained certain achievement,however,many studies have shown that esophageal cancer factors exist in many aspects,mainly with the nitrosamines in the water,food,pickles and sauerkraut of mycotoxin,lack of some trace elements in the food,people some unhealthy diet(like to eat hot food,hot food,etc.)and living habits and other related factors.In addition,the treatment of esophageal cancer is the most main means is still surgery,although surgery and the treatment progress in recent years,however,the 5-year survival rate of esophageal patients at home and abroad is<20%.Some neoadjuvant therapy and adjuvant therapy are also used in esophageal cancer treatment,but there is no standardized guide and strong evidence to date.We face great challenges in the treatment of esophageal cancer.Therefore,we need to find out more effective tumor molecular markers to study the development and biological characteristics of esophageal cancer from the cellular molecular level.To help us to strengthen the prevention and early diagnosis of esophageal cancer cells,targeted therapy,according to different patients,choose suitable for individualized treatment plan,improve long-term survival rate and better quality of life.In the basic research of esophageal cancer,the genes and signaling pathways of esophageal cancer have been paid more and more attention,and it has provided an important theoretical basis for the development of esophageal cancer targeted therapy.Membrane associated protein(Annexins,ANX)is a kind of have the Ca +dependent protein family,can be combined with negatively charged membrane phospholipids,ANX participate in a variety of physiological functions in the body,including the formation of cell division and proliferation,membrane ion channel,the inhibition of phospholipase A2,swallow and spit the cell function and interaction between cells,etc.ANX family,found in recent years in the tumor plays a more and more important role in the occurrence and development of Annexin A1 as ANX family of one of the earliest discovered family proteins,Annexin Al,as an important multifunctional protein abnormal expression in many tumor tissues,in breast cancer,gastric cancer,esophageal squamous carcinoma,prostate cancer,head and neck cancer,oral cancer,the expression of Annexin A1 cut or lack of,on the contrary,in adenocarcinoma of the lung cancer,pancreatic cancer,esophagus,bladder,kidney,pituitary carcinoma,the expression of Annexin Al is enhanced,two kinds of different pathological types of esophageal cancer in the expression of Annexin A1,there are differences in esophageal squamous carcinoma and adenocarcinoma of the identification and diagnosis plays an important role.The WNT/beta-catenin signaling pathway is the most classic of the WNT pathway,and plays an important role in human body transcription factors and signaling molecules and molecular pathways in and out of various cells.In cell proliferation and tissue organ played an important role in regulation of each link,in recent years,a large number of studies have found that WNT/beta-catenin pathway epidermal cells and tumor cells-interstitial cells(EMT)have close relations,calcium sticky element(cadherin)as the EMT plays an important role,and its expression has close relationship with tumor.E cadherin(E-calcium sticky grain)with beta cells-catenin form stable E-cadherin/beta-catenin compounds,the compounds can be very good maintain normal epithelial morphology,also play an important role in cell adhesion,beta-catenin main regulatory role in the complexes.A large number of cytokines can lead to beta-catenin phosphorylation,phosphorylation of beta-catenin will reduce the stability of the complexes,resulting in tumor cell adhesion between connected loosely,leading to a tumor cell invasion and metastasis ability enhancement.Some scholars study showed that the expression of Annexin A1 in esophageal squamous carcinoma is the expression of normal esophageal tissue is cut,and cause the occurrence of the EMT the biological behavior of tumor cells,but the inner mechanism of biology is not deep.Through our previous experiments,tissue samples for testing in patients with esophageal squamous cell carcinomas,and found that the lower expression of Annexin A1,we proposed by tissue section,esophageal squamous cancer cells and nude mice animal experiments these aspects to test the Annexin Al,in-depth understanding of Annexin A1 in esophageal squamous cell carcinomas of the role of the developing,to understand the mechanism of action of Annexin A1 and its molecular basis.Methods:1.The expression of Annexin A1 protein in the organization;2.In vitro cell function test verified the influence of Annexin A1 protein on malignant phenotype of esophageal squamous cell carcinoma;3.The effects of Annexin A1 protein on tumor formation ability in esophageal squamous cell carcinoma cells were verified by nude mice.4.The study on the relationship between Annexin A1 protein and WNT/beta-catenin signaling pathway was verified by the protein immunoimprinting method.Results:1.We found that the expression of Annexin A1 protein in esophageal squamous cell carcinoma was lower than that of normal esophageal tissue.2.The ability of cell proliferation,cloning and migration was inhibited after the expression of Annexin A1 protein kyse-510-annexin A1 overexpression group of esophageal squamous cell carcinoma.At the same time,the proliferation,cloning and migration of cells in the kyse-150-sh19 esophageal squamous cell carcinoma cells that interfered with Annexin A1 protein were enhanced.3.Interfering with the expression of Annexin Al protein can promote the tumor formation ability of Kyse150 cells in nude mice.4.Interfering with the expression of Annexin A1 protein can promote the expression of beta-catenin in the WNT/beta-catenin pathway and inhibit the expression of gs3k-beta and DKK1 protein.In contrast,overexpression of Annexin A1 can inhibit the expression of beta-catenin in the WNT/beta-catenin pathway and promote the expression of gs3k-alpha and DKK1.At the same time,the Annexin A1 protein change,led to the change of the EMT markers,with the expression of Annexin A1 protein cut,E-Cadherin decline,the increase of N-Cadherin and Snail,raised Annexin A1 protein expression,E-Cadherin rise,N-Cadherin and Snail.Conclusion:1.Annexin al protein showed low expression in esophageal squamous carcinoma.2.The low expression level of Annexin al promoted the transformation of esophageal squamous cell carcinoma to malignant phenotype.3.Annexin al protein may induce the occurrence of EMT biological behavior of esophageal squamous cell carcinoma cells by affecting the expression of WNT/beta-catenin pathway proteins. |
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