Laboratory of Molecular Cell Biology and Tumor Biology

Beijing, China

Laboratory of Molecular Cell Biology and Tumor Biology

Beijing, China

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Zhan J.,Peking University | Zhan J.,Laboratory of Molecular Cell Biology and Tumor Biology | Yang M.,Peking University | Yang M.,Laboratory of Molecular Cell Biology and Tumor Biology | And 12 more authors.
Science China Life Sciences | Year: 2014

Kindlin-2 functions in the maintenance of homeostasis and in human diseases. This study investigated the interrelationship between Kindlin-2 expression in tissues and the corresponding germ layers from which these tissues originated. Kindlin-2 expression was examined in normal adult human organs and human cancer tissues by immunohistochemical analyses. Analysis of Kindlin-2 mRNA levels in adult human organs in the Oncomine dataset revealed Kindlin-2 is highly expressed in mesoderm-derived organs. However, Kindlin-2 was negative or weakly expressed in endoderm/ectoderm-derived organs. Interestingly, the abnormal expression of Kindlin-2 was observed in a variety of human cancers. In agreement with its expression profile in humans, Kindlin-2 was also highly expressed in mesoderm-derived organs in mouse embryos with the exception of strong Kindlin-2 expression in ectoderm-derived spinal cord and ganglia, tissues that are highly mobile during embryonic development. Importantly, we demonstrated the expression level of Kindlin-2 in adult organs correlated with their embryonic dermal origins and deregulation of Kindlin-2 in tissues is associated with tumor progression. This finding will help us understand the dual role of Kindlin-2 in the regulation of tumor progression and embryonic development. © 2014 The Author(s).


Zhan J.,Peking University | Zhan J.,Laboratory of Molecular Cell Biology and Tumor Biology | Wang P.,Peking University | Wang P.,Laboratory of Molecular Cell Biology and Tumor Biology | And 8 more authors.
Histopathology | Year: 2015

Aims: HoxB9, as a Hox family member, is known to play important roles in embryonic development. Recent studies showed that HoxB9 is engaged in cancer progression. However, the role of Hoxb9 in lung adenocarcinoma is unknown. The purpose of this study is to investigate the expression and prognostic value of HoxB9 in patients with lung adenocarcinoma. Methods and results: The localization and expression of HoxB9 in lung adenocarcinoma were examined by immunohistochemistry. The correlation between HoxB9 expression levels with patient survival was assessed by Kaplan-Meier analysis. The epithelial-mesenchymal transition (EMT) markers and migratory ability were evaluated in HoxB9 up- and down-regulated H1299 lung adenocarcinoma cells. HoxB9 was found to be localized predominantly in the cell nuclei and expressed in 21.3% of lung adenocarcinomas. A significant increase in HoxB9 intensity in the high stage of lung adenocarcinoma was observed (P < 0.01). Increased expression of HoxB9 was related to T classification, more lymph node metastasis and a shorter patient overall survival (P < 0.05). However, the expression level of HoxB9 was not correlated with age and gender. Functionally, HoxB9 up-regulated EMT-related molecules and promoted cell migration in H1299 cells. Conclusion: High expression of HoxB9 is a prognostic marker for lung adenocarcinoma patients. © 2014 John Wiley & Sons Ltd.


Zhan J.,Peking University | Zhan J.,Laboratory of Molecular Cell Biology and Tumor Biology | Song J.,Peking University | Song J.,Laboratory of Molecular Cell Biology and Tumor Biology | And 10 more authors.
Cancer Letters | Year: 2015

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths with no effective therapeutics. Invasion and metastasis are the major characteristics of PDAC. However, mechanisms underlying PDAC invasion and metastasis are elusive. In this report, we found that Kindlin-2 is a target protein of transforming growth factor β (TGF-β) signaling and is upregulated by TGF-β1 in PDAC cells. TGF-β1-upregulated Kindlin-2 promotes PDAC cell growth, migration and invasion, whereas Kindlin-2 upregulates transforming growth factor receptor I (TβRI), a key component of TGF-β signaling. Thereby Kindlin-2 and TGF-β signaling constitute a positive feedback loop. Mechanistically, Kindlin-2 promotes PDAC progression by downregulation of HOXB9 and E-cadherin. For clinical relevance, enhanced expression of Kindlin-2 predicts a poor overall survival for PDAC patients. Gene expression levels of Kindlin-2, TGF-β, TβRI and HOXB9 are all correlated with the overall survival of PDAC patients in an Oncomine dataset. Taken together, our findings demonstrated that TGF-β1-induced Kindlin-2 expression promotes PDAC progression by downregulation of HOXB9 and E-cadherin. © 2015 Elsevier Ireland Ltd.


PubMed | Key Laboratory of Carcinogenesis and Translational Research, Laboratory of Molecular Cell Biology and Tumor Biology and Peking University
Type: | Journal: OncoTargets and therapy | Year: 2016

Recent studies showed that muscarinic acetylcholine receptor 3 (M3), as a muscarinic acetylcholine receptor family member that plays an important role in normal physiological function, is engaged in cancer progression. However, the role of M3 in pancreatic ductal adenocarcinoma (PDAC) is not known. The aim of this study is to investigate the expression and prognostic value of M3 in patients with PDAC.The localization and expression of M3 in PDAC were examined by immunohistochemistry. VAChT was employed to detect parasympathetic nerve fibers in the corresponding M3 PDAC tissues. The correlation between M3 expression and patients survival was assessed by Kaplan-Meier analysis.M3 was discovered predominantly localized in the cell cytoplasm and expressed in all specimens of PDAC patients. Significant correlation was noted between increased M3 intensity and high grade of PDAC (High expression of M3 is a prognostic marker for PDAC.


Yuan S.,China Agricultural University | Yuan S.,Tianjin Medical University | Yuan S.,Southwest University | Li F.,China Agricultural University | And 8 more authors.
PLoS Genetics | Year: 2015

Hair follicles (HF) undergo precisely regulated recurrent cycles of growth, cessation, and rest. The transitions from anagen (growth), to catagen (regression), to telogen (rest) involve a physiological involution of the HF. This process is likely coordinated by a variety of mechanisms including apoptosis and loss of growth factor signaling. However, the precise molecular mechanisms underlying follicle involution after hair keratinocyte differentiation and hair shaft assembly remain poorly understood. Here we demonstrate that a highly conserved microRNA, miR-22 is markedly upregulated during catagen and peaks in telogen. Using gain- and loss-of-function approaches in vivo, we find that miR-22 overexpression leads to hair loss by promoting anagen-to-catagen transition of the HF, and that deletion of miR-22 delays entry to catagen and accelerates the transition from telogen to anagen. Ectopic activation of miR-22 results in hair loss due to the repression a hair keratinocyte differentiation program and keratinocyte progenitor expansion, as well as promotion of apoptosis. At the molecular level, we demonstrate that miR-22 directly represses numerous transcription factors upstream of phenotypic keratin genes, including Dlx3, Foxn1, and Hoxc13. We conclude that miR-22 is a critical post-transcriptional regulator of the hair cycle and may represent a novel target for therapeutic modulation of hair growth. © 2015 Yuan et al.


PubMed | Philadelphia University, Chongqing Academy of Animal Science, Tianjin Medical University, Laboratory of Molecular Cell Biology and Tumor Biology and China Agricultural University
Type: Journal Article | Journal: PLoS genetics | Year: 2015

Hair follicles (HF) undergo precisely regulated recurrent cycles of growth, cessation, and rest. The transitions from anagen (growth), to catagen (regression), to telogen (rest) involve a physiological involution of the HF. This process is likely coordinated by a variety of mechanisms including apoptosis and loss of growth factor signaling. However, the precise molecular mechanisms underlying follicle involution after hair keratinocyte differentiation and hair shaft assembly remain poorly understood. Here we demonstrate that a highly conserved microRNA, miR-22 is markedly upregulated during catagen and peaks in telogen. Using gain- and loss-of-function approaches in vivo, we find that miR-22 overexpression leads to hair loss by promoting anagen-to-catagen transition of the HF, and that deletion of miR-22 delays entry to catagen and accelerates the transition from telogen to anagen. Ectopic activation of miR-22 results in hair loss due to the repression a hair keratinocyte differentiation program and keratinocyte progenitor expansion, as well as promotion of apoptosis. At the molecular level, we demonstrate that miR-22 directly represses numerous transcription factors upstream of phenotypic keratin genes, including Dlx3, Foxn1, and Hoxc13. We conclude that miR-22 is a critical post-transcriptional regulator of the hair cycle and may represent a novel target for therapeutic modulation of hair growth.

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