Kindlin-2, an integrin-interacting protein, regulates breast cancer progression. However, currently, no animal model to study the role of Kindlin-2 in the carcinogenesis of mammary gland is available. We established a...Kindlin-2, an integrin-interacting protein, regulates breast cancer progression. However, currently, no animal model to study the role of Kindlin-2 in the carcinogenesis of mammary gland is available. We established a Kindlin-2 transgenic mouse model using a mammary gland-specific promoter, mammary tumor virus(MMTV) long terminal repeat(LTR). Kindlin-2 was overexpressed in the epithelial cells of the transgenic mice. The mammary gland ductal trees were found to grow faster in MMTV-Kindlin-2 transgenic mice than in control mice during puberty. Kindlin-2 promoted mammary gland growth as indicated by more numerous duct branches and larger lumens, and more alveoli were formed in the mammary glands during pregnancy under Kindlin-2 overexpression. Importantly, mammary gland-specific expression of Kindlin-2 induced tumor formation at the age of 55 weeks on average. Additionally, the levels of estrogen receptor and progesterone receptor were decreased, whereas human epidermal growth factor receptor 2 and β-catenin were upregulated in the Kindlin-2-induced mammary tumors. These findings demonstrated that Kindlin-2 induces mammary tumor formation via activation of the Wnt signaling pathway.展开更多
Basal-like breast cancer with a luminal progenitor gene expression profile is an aggressive subtype of breast cancer with a poorer prognosis compared with other subtypes.However,genes that specifically promote basal-l...Basal-like breast cancer with a luminal progenitor gene expression profile is an aggressive subtype of breast cancer with a poorer prognosis compared with other subtypes.However,genes that specifically promote basal-like breast cancer development remain largely unknown.Here,we report that a novel gene C1orf106 plays an important role in maintaining the feature of basal-like/luminal progenitors.C1orf106 is frequently amplified and overexpressed in basal-like breast cancer and is associated with a poor outcome in patients.In human TCGA database,C1orf106 expression was correlated with upregulation of ELF5 and downregulation of GATA3,two transcription factors that regulate mammary gland stem cell fate.Enhanced expression of C1orf106 promotes tumor progression and expression of basal-like/luminal progenitor marker ELF5;depletion of C1orf106 suppresses tumorigenesis and expression of basal-like/luminal progenitor marker GATA3.These findings suggest that C1orf106 maintains the basal-like/luminal progenitor character through balancing the expression of ELF5 and GATA3.Taken together,we demonstrated that C1orf106 is an important regulator for basal-like/luminal progenitors and targeting C1orf106 is of therapeutic value for breast cancer.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
Pancreatic ductal adenocarcinoma(PDAC)is the ninth most common human malignancy and the sixth leading cause of cancer-related death in China.AcK27-HOXB9 is a newly identified HOXB9 post-transcriptional modification th...Pancreatic ductal adenocarcinoma(PDAC)is the ninth most common human malignancy and the sixth leading cause of cancer-related death in China.AcK27-HOXB9 is a newly identified HOXB9 post-transcriptional modification that can predict the outcome in lung adenocarcinoma and colon cancer well.However,the role of AcK27-HOXB9 in PDAC is unclear.The present study aims to investigate the differential diagnostic role of patients with AcK27-HOXB9 PDAC.Tissue microarrays consisting of 162 pancreatic tumor tissue samples from patients with PDAC and paired normal subjects were used to examine HOXB9 and AcK27-HOXB9 levels and localizations by immunohistochemical analysis and Western blot assay,respectively.HOXB9 was upregulated(P<0.0001),and AcK27-HOXB9(P=0.0023)was downregulated in patients with PDAC.HOXB9 promoted(P=0.0115),while AcK27-HOXB9(P=0.0279)inhibited PDAC progression.AcK27-HOXB9 predicted favorable outcome in patients with PDAC(P=0.0412).AcK27-HOXB9 also suppressed PDAC cell migration in a cell migration assay.The results of this study showed that HOXB9 promoted and AcK27-HOXB9 suppressed PDAC progression.The determination of ratio between HOXB9 and AcK27-HOXB9 exhibited potential diagnostic value in patients with PDAC.展开更多
基金supported by grants from the Ministry of Science and Technology of China (2016YFC1302103, 2015CB553906, and 2013CB910501)the National Natural Science Foundation of China (81730071, 81230051, 81472734, and 31170711)+3 种基金the Beijing Natural Science Foundation (7120002 and 7171005)the 111 Project of the Ministry of Education, grants from Peking University (BMU20120314 and BMU20130364)a Leading Academic Discipline Project of Beijing Education Bureau to H.Z.supported by a grant from the National Natural Science Foundation of China (81773199) to J.Z
文摘Kindlin-2, an integrin-interacting protein, regulates breast cancer progression. However, currently, no animal model to study the role of Kindlin-2 in the carcinogenesis of mammary gland is available. We established a Kindlin-2 transgenic mouse model using a mammary gland-specific promoter, mammary tumor virus(MMTV) long terminal repeat(LTR). Kindlin-2 was overexpressed in the epithelial cells of the transgenic mice. The mammary gland ductal trees were found to grow faster in MMTV-Kindlin-2 transgenic mice than in control mice during puberty. Kindlin-2 promoted mammary gland growth as indicated by more numerous duct branches and larger lumens, and more alveoli were formed in the mammary glands during pregnancy under Kindlin-2 overexpression. Importantly, mammary gland-specific expression of Kindlin-2 induced tumor formation at the age of 55 weeks on average. Additionally, the levels of estrogen receptor and progesterone receptor were decreased, whereas human epidermal growth factor receptor 2 and β-catenin were upregulated in the Kindlin-2-induced mammary tumors. These findings demonstrated that Kindlin-2 induces mammary tumor formation via activation of the Wnt signaling pathway.
基金supported by the Ministry of Science and Technology of China (2016YFC1302103 and 2015CB553906)the National Natural Science Foundation of China (81230051, 81472734,31170711, 81321003, and 30830048)+3 种基金the Beijing Natural Science Foundation (7120002)the 111 Project of the Ministry of Education, Peking University (BMU2018JC004, BMU20120314, and BMU20130364)a Leading Academic Discipline Project of Beijing Education Bureau to H.Za grant from the National Natural Science Foundation of China (81773199) to J.Z
文摘Basal-like breast cancer with a luminal progenitor gene expression profile is an aggressive subtype of breast cancer with a poorer prognosis compared with other subtypes.However,genes that specifically promote basal-like breast cancer development remain largely unknown.Here,we report that a novel gene C1orf106 plays an important role in maintaining the feature of basal-like/luminal progenitors.C1orf106 is frequently amplified and overexpressed in basal-like breast cancer and is associated with a poor outcome in patients.In human TCGA database,C1orf106 expression was correlated with upregulation of ELF5 and downregulation of GATA3,two transcription factors that regulate mammary gland stem cell fate.Enhanced expression of C1orf106 promotes tumor progression and expression of basal-like/luminal progenitor marker ELF5;depletion of C1orf106 suppresses tumorigenesis and expression of basal-like/luminal progenitor marker GATA3.These findings suggest that C1orf106 maintains the basal-like/luminal progenitor character through balancing the expression of ELF5 and GATA3.Taken together,we demonstrated that C1orf106 is an important regulator for basal-like/luminal progenitors and targeting C1orf106 is of therapeutic value for breast cancer.
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.
基金supported by grants from the Ministry of Science and Technology of China(Nos.2016YFC1302103 and 2015CB553906)the National Natural Science Foundation of China(Nos.81730071,81230051,81472734,and 31170711)+1 种基金the Beijing Natural Science Foundation(Nos.7120002 and 7171005)This work was also supported by a grant from the National Natural Science Foundation of China(No.81773199)to Jun Zhan.
文摘Pancreatic ductal adenocarcinoma(PDAC)is the ninth most common human malignancy and the sixth leading cause of cancer-related death in China.AcK27-HOXB9 is a newly identified HOXB9 post-transcriptional modification that can predict the outcome in lung adenocarcinoma and colon cancer well.However,the role of AcK27-HOXB9 in PDAC is unclear.The present study aims to investigate the differential diagnostic role of patients with AcK27-HOXB9 PDAC.Tissue microarrays consisting of 162 pancreatic tumor tissue samples from patients with PDAC and paired normal subjects were used to examine HOXB9 and AcK27-HOXB9 levels and localizations by immunohistochemical analysis and Western blot assay,respectively.HOXB9 was upregulated(P<0.0001),and AcK27-HOXB9(P=0.0023)was downregulated in patients with PDAC.HOXB9 promoted(P=0.0115),while AcK27-HOXB9(P=0.0279)inhibited PDAC progression.AcK27-HOXB9 predicted favorable outcome in patients with PDAC(P=0.0412).AcK27-HOXB9 also suppressed PDAC cell migration in a cell migration assay.The results of this study showed that HOXB9 promoted and AcK27-HOXB9 suppressed PDAC progression.The determination of ratio between HOXB9 and AcK27-HOXB9 exhibited potential diagnostic value in patients with PDAC.
