Mutations of integrin-interacting protein Kindlin-1 cause Kindler syndrome and deregulation of Kindlin-1 is implicated in human cancers. The Kindlin-1-related diseases are confined in limited tissue types. However, Ki...Mutations of integrin-interacting protein Kindlin-1 cause Kindler syndrome and deregulation of Kindlin-1 is implicated in human cancers. The Kindlin-1-related diseases are confined in limited tissue types. However, Kindlin-1 tissue distribution and the dogma that governs Kindlin-1 expression in normal human body are elusive. This study examined Kindlin-1 expression in normal human adult organs, human and mouse embryonic organs by immunohistochemical analyses. We identified a general principle that the level of Kindlin-1 expression in tissues is tightly correlated with the corresponding germ layers from which these tissues originate. We compared the expression of Kindlin-1 with Kindlin-2 and found that Kindlin-1 is highly expressed in epithelial tissues derived from ectoderm and endoderm, whereas Kindlin-2 is mainly expressed in mesoderm-derived tissues. Likewise, Kindlin-1 was also found highly expressed in endoderm/ectoderm-derived tissues in human and mouse embryos. Our findings indicate that Kindlin-1 may play an importance role in the development of endoderm/ectoderm related tissues.展开更多
Esophageal cancer （EC） is one of the most lethal malignancies in China, but the etiology and risk factors remain unclear. The integrin-interacting proteins Kindlin-1 and Kindlin-2 are focal adhesion molecules that a...Esophageal cancer （EC） is one of the most lethal malignancies in China, but the etiology and risk factors remain unclear. The integrin-interacting proteins Kindlin-1 and Kindlin-2 are focal adhesion molecules that activate transmembrane receptor integrins and regulate tumor cell growth, invasion, and metastasis. Here, we report that Kindlin-1 and Kindlin-2 are differentially expressed among Chinese EC patients. For this, Kindlin-1 and Kindlin-2 expression was evaluated in 220 EC patients by immunohistochemistry （IHC） and found to be correlated with the EC progression, along with a variety of epidemiologic parameters, including smoking, family EC history, and EC invasion status. Moreover, data downloaded from the Oncomine database revealed that both Kindlin- 1 and Kindlin-2 were upregulated in ECs compared with normal esophageal tissues; although Kindlin-1 was highly expressed in well-differentiated tumors, whereas Kindlin-2 was more prevalent in poorly differentiated tumors. Collectively, these data suggest that Kindlin-1 may inhibit, while Kindlin-2 may promote, EC progression. This study, for the first time, linked the expression of Kindlin-1 and Kindlin-2 with EC family genetic background and living habits, which may help further our understanding of the various causes of EC.展开更多
基金supported by the National Natural Science Foundation of China(81301802,81230051,30830048,31170711)Grant of Ministry of Science and Technology of China(2013CB910501,2010CB912203,2010CB529402)+3 种基金Program for Introducing Talents of Discipline to Universities(111 Project)of Ministry of EducationBeijing Natural Science Foundation(7120002)Peking University grants(BMU20120314,BMU20130364,BMU20130373)a Leading Academic Discipline Project of Beijing Education Bureau
文摘Mutations of integrin-interacting protein Kindlin-1 cause Kindler syndrome and deregulation of Kindlin-1 is implicated in human cancers. The Kindlin-1-related diseases are confined in limited tissue types. However, Kindlin-1 tissue distribution and the dogma that governs Kindlin-1 expression in normal human body are elusive. This study examined Kindlin-1 expression in normal human adult organs, human and mouse embryonic organs by immunohistochemical analyses. We identified a general principle that the level of Kindlin-1 expression in tissues is tightly correlated with the corresponding germ layers from which these tissues originate. We compared the expression of Kindlin-1 with Kindlin-2 and found that Kindlin-1 is highly expressed in epithelial tissues derived from ectoderm and endoderm, whereas Kindlin-2 is mainly expressed in mesoderm-derived tissues. Likewise, Kindlin-1 was also found highly expressed in endoderm/ectoderm-derived tissues in human and mouse embryos. Our findings indicate that Kindlin-1 may play an importance role in the development of endoderm/ectoderm related tissues.
基金supported by the Ministry of Science and Technology of China (2016YFC1302103, 2015CB553906. 2013CB910501)the National Natural Science Foundation of China (81230051, 81472734, 31170711, 81321003, 81301802, 30830048)+2 种基金Beijing Natural Science Foundation (7120002)the 111 Project of the Ministry of Education, Peking University (BMU20120314, BMU20130364)a Leading Academic Discipline Project of Beijing Education Bureau to Hongquan Zhang
文摘Esophageal cancer （EC） is one of the most lethal malignancies in China, but the etiology and risk factors remain unclear. The integrin-interacting proteins Kindlin-1 and Kindlin-2 are focal adhesion molecules that activate transmembrane receptor integrins and regulate tumor cell growth, invasion, and metastasis. Here, we report that Kindlin-1 and Kindlin-2 are differentially expressed among Chinese EC patients. For this, Kindlin-1 and Kindlin-2 expression was evaluated in 220 EC patients by immunohistochemistry （IHC） and found to be correlated with the EC progression, along with a variety of epidemiologic parameters, including smoking, family EC history, and EC invasion status. Moreover, data downloaded from the Oncomine database revealed that both Kindlin- 1 and Kindlin-2 were upregulated in ECs compared with normal esophageal tissues; although Kindlin-1 was highly expressed in well-differentiated tumors, whereas Kindlin-2 was more prevalent in poorly differentiated tumors. Collectively, these data suggest that Kindlin-1 may inhibit, while Kindlin-2 may promote, EC progression. This study, for the first time, linked the expression of Kindlin-1 and Kindlin-2 with EC family genetic background and living habits, which may help further our understanding of the various causes of EC.
