Beijing Key Laboratory for Cancer Invasion and Metastasis Research

Beijing, China

Beijing Key Laboratory for Cancer Invasion and Metastasis Research

Beijing, China
SEARCH FILTERS
Time filter
Source Type

Zhao H.,Capital Medical University | Zhao H.,Beijing Key Laboratory for Cancer Invasion and Metastasis Research | Zhao H.,University of Cardiff | Yu H.,Capital Medical University | And 8 more authors.
Oncology Reports | Year: 2016

The junctional adhesion molecule B (JAM-B) is a multifunctional transmembrane protein, which belongs to the immunoglobulin superfamily (IgSF). JAM-B is localized to cell-cell contacts and enriched at cell junctions in epithelial and endothelial cells, as well as on the surface of erythrocytes, leukocytes, and platelets. Recent research in this field has shown that JAM-B plays an important role in numerous cellular processes, such as tight junction assembly, spermatogenesis, regulation of paracellular permeability, leukocytic transmigration, angiogenesis, tumor metastasis and cell proliferation. This study provides a new research direction for the diagnosis and treatment of relevant diseases. In this review, we briefly focus on what is currently known about the structure, function, and mechanism of JAM-B, with particular emphasis on cancer. © 2016, Spandidos Publications. All rights reserved.


Yu H.,Capital Medical University | Yu H.,Beijing Key Laboratory for Cancer Invasion and Metastasis Research | Ge Z.,Capital Medical University | Ge Z.,Beijing Key Laboratory for Cancer Invasion and Metastasis Research | And 10 more authors.
RSC Advances | Year: 2016

Ehm2, which belongs to the FERM superfamily, is a metastasis-associated protein. However, its function in cancer metastasis and the associated molecular mechanism is not definitely clear. Alternative splicing is an important biological step during mRNA processing and has been reported to be related with many diseases including cancers. Ehm2 has two transcript variants. Transcript variant 1(Ehm2/1) encodes isoform 1 of 518 amino acids, while transcript variant 2(Ehm2/2) encodes isoform 2 of 913 amino acids. In this study, we found that Ehm2/1 was the main transcript variant in the MCF-7 breast cancer cell line. Forced expression of Ehm2/1 upregulated the total protein amount but had no effect on the mRNA levels of β-catenin. The increased β-catenin was found to be dominantly located at the cell membrane. Meanwhile, knockdown of Ehm2/1 in MCF-7 cells decreased the total protein amount but not the mRNA levels of β-catenin. Further results showed that Ehm2/1 interacted with β-catenin and colocalized with it at the cell membrane. E-cadherin, a partner of β-catenin in cadherin-catenin complexes, was also upregulated by the overexpression of Ehm2/1 and also colocalized with it at the cell membrane. Meanwhile, overexpression of Ehm2/1 inhibited the migration ability of MCF-7 cells. These results suggested that Ehm2/1 may render β-catenin at the cell membrane by interacting with β-catenin and E-cadherin. © 2016 The Royal Society of Chemistry.


Zhao H.,University of Cardiff | Zhao H.,Capital Medical University | Zhao H.,Beijing Key Laboratory for Cancer Invasion and Metastasis Research | Martin T.A.,University of Cardiff | And 9 more authors.
Anticancer Research | Year: 2016

Background/Aim: The ribosomal S6 protein kinase (RSK) family is an important effector of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) that could influence tumour metastasis by phosphorylating proteins in both the nuclear and cytoplasmic compartments. Aberrant expression of RSK is evident in certain malignancies but the role played by RSK in breast cancer is still not clear. This study aimed to examine the expression of RSK in human breast cancer specimens and its role to breast cancer metastasis. Materials and Methods: The expression of RSK1 to-3 were separately examined in human breast cancer tissues (normal, n=33; cancer, n=112) using quantitative real-time polymerase chain reaction (Q-PCR) and immunohistochemistry. Migration and adhesion of breast cancer cells treated with the RSK inhibitor SL0101 were investigated by electric cell impedance sensing (ECIS). The effect on growth and invasion of RSK1-3 was then investigated using in vitro models. Results: The clinical data and immunohistochemistry revealed that expression of RSK1 and RSK3 were less in tumour tissues than normal. mRNA expression of RSK2 was negatively correlated with grade, TNM staging, and survival rate. SL0101 inhibited adhesion of the MCF-7 and MDA-231 breast cancer cell lines. SL0101 suppressed MDA-231 invasion and the alternate RSK inhibitor BRD7389 inhibited the invasion of MCF-7 and MDA-231 cells. Conclusion: RSK1 and 3 but not RSK2 are down-regulated in breast tumour and are associated with disease progression. RSK may be a key component in the progression and metastasis of breast cancer.


Zhao H.,Capital Medical University | Zhao H.,Beijing Key Laboratory for Cancer Invasion and Metastasis Research | Zhao H.,University of Cardiff | Yu H.,Capital Medical University | And 9 more authors.
International Journal of Oncology | Year: 2016

The junctional adhesion molecule (JAMs) family belongs to the immunoglobulin subfamily involved in the formation of tight junctions (TJ) in both endothelial and epithelial cells. Aberrant expression of JAM-2 is associated with cancer progression but little work has been carried out in discovering how this affects changes in cell behaviour. The present study aimed to examine the expression of JAM-2 in human colon cancer specimens and cell lines and its role in the development of colon cancer. JAM-2 expression in human colon cancer specimens (normal, n=75; cancer, n=94) and cell lines was analysed using quantitative real-time PCR and conventional RT-PCR. Colon cancer cells were stably transfected with a mammalian expression vector to overexpress JAM-2-Flag. The effect on growth, adhesion and migration following overexpression of JAM-2 was then investigated using in vitro models. TJ function was assessed using a transepithelial resistance assay (TER, with an EVOM voltammeter). JAM-2 was lowly expressed in colon cancer cells such as RKO, HT115. JAM-2 overexpression in RKO cells (RKO-JAM-2) and HT115 cells (HT115-JAM-2) showed retarded adhesion (P<0.05). An in vivo tumour model showed that RKO-JAM-2 had significantly reduced growth (P<0.05), invasion (P<0.05) and migration (P<0.05) as well as in HT115-JAM-2, except on proliferation and migration. Expression of JAM-2 resulted in a significant increase in TER and decrease in permeability of polarized monolayers (P<0.05). Further analysis of JAM-2 transcript levels against clinical aspects demonstrated that the decreasing JAM-2 expression correlated to disease progression, metastasis and poor survival. Taken together, JAM-2 may function as a putative tumour suppressor in the progression and metastasis of colorectal cancer.

Loading Beijing Key Laboratory for Cancer Invasion and Metastasis Research collaborators
Loading Beijing Key Laboratory for Cancer Invasion and Metastasis Research collaborators