Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation

Tianjin, China

Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation

Tianjin, China
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Li X.,Nankai University | Li X.,Beijing Health Vocational College | Chen S.,Nankai University | Chen S.,National Center for Toxicological Research (NCTR) | And 8 more authors.
Clinical Laboratory | Year: 2014

Background: Recent study demonstrated the important contribution of SOX2 to tumorigenesis and metastasis properties of various types of cancers and strongly supported the concept that SOX2 can be used as an effective marker for diagnosis and predicting prognosis of cancer patients. However, our previous RNA-Seq results from human lung cancer cell line A549 showed that some oncogenes, including FOXA1 are negatively regulated by SOX2. Methods: To further verify the transcriptional regulation effect of SOX2 on FOXA1 and elucidate its application in the diagnosis of human lung and breast cancer, we performed real-time RT-PCR and Western blotting to test the regulation effect of SOX2 on the expression of FOXA1 gene. OncoPrint analysis was used to reveal the alteration of SOX2 and FOXA1 genes in breast invasive carcinoma cases and lung squamous cell carcinoma cases from the Cancer Genome Atlas (TCGA) data portal. Immunohistochemistry staining was performed to test the expression of SOX2 and FOXA1 in human breast and lung carcinoma. Results: The results showed that there is an inhibitory effect of SOX2 on the expression of FOXA1 gene. In addition, these two genes are altered in 5.8% of 484 breast invasive carcinoma cases and 46.4% of 179 lung squamous cell carcinoma cases from the Cancer Genome Atlas (TCGA) data portal, which showed an increased percentage of carcinoma cases when compared with single gene alteration. Immunohistochemistry staining of SOX2 and FOXA1 in human breast and lung carcinoma further revealed the mutual complementary effect of these two proteins in the diagnosis of carcinoma. Conclusions: Our study revealed SOX2 as a negative upstream regulator for FOXA1 gene and demonstrated SOX2 and FOXA1 as effective dual markers in improving the diagnosis efficiency for human lung and breast tumor.

Zhao S.,Nankai University | Liu W.,Tianjin Entry Exit Inspection and Quarantine Bureau | Li Y.,Nankai University | Liu P.,First Central Hospital | And 7 more authors.
PLoS ONE | Year: 2016

The molecular defects which lead to multistep incidences of human T-cell leukemia have yet to be identified. The DNA-binding protein Helios (known as IKZF2), a member of the Ikaros family of Krüppel-like zinc-finger proteins, functions pivotally in T-cell differentiation and activation. In this study, we identify three novel short Helios splice variants which are T-cell leukemic specific, and demonstrate their dominant-negative function. We then test the cellular localization of distinct Helios isoforms, as well as their capability to form heterodimer with Ikaros, and the association with complexes comprising histone deacetylase (HDAC). In addition, the ectopic expression of T-cell leukemic Helios isoforms interferes with T-cell proliferation and apoptosis. The gene expression profiling and pathway analysis indicated the enrichment of signaling pathways essential for gene expression, translation, cell cycle checkpoint, and response to DNA damage stimulus. These data indicate the molecular function of Helios to be involved in the leukemogenesis and phenotype of T-cell leukemia, and also reveal Helios deregulation as a novel marker for T-cell leukemia. © 2016 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Li X.,Nankai University | Xu Y.,Nankai University | Chen Y.,Nankai University | Chen S.,Nankai University | And 9 more authors.
Cancer Letters | Year: 2013

SOX2 was reported to promote metastasis in various tumor tissues; however the underlying mechanisms remain elusive. Here, we disclosed that SOX2 improves metastasis of breast and prostate cancer cells by promoting epithelial-to-mesenchymal transition (EMT) through WNT/β-catenin, but not TGF-β or Snail1 signaling. Dual luciferase assay and chromatin immunoprecipitation revealed activation and binding of SOX2 on promoter region of β-catenin. In addition, SOX2 affects the protein expression levels of DKK3, DVL1 and DVL3, which are regulators or downstream molecules of WNT signaling. Taken together, our findings demonstrated β-catenin as one of vital downstream molecules that mediate the EMT induced by SOX2. © 2013 Elsevier Ireland Ltd.

Mou W.,Nankai University | Mou W.,Capital Medical University | Mou W.,Chinese PLA General Hospital | Xu Y.,Nankai University | And 13 more authors.
Cancer Letters | Year: 2015

Transcriptional factor Sox2 promotes tumor metastasis; however its regulatory effect on tumor-associated macrophages (TAMs, M2 phenotype) has not been defined. This study disclosed concomitant expression of TAMs marker-CD163 with SOX2 in human breast cancer and showed that Sox2 in breast cancer cells promotes recruitment of TAMs with altered expression of multiple chemokines, including MIP-1α, ICAM-1 etc. and activation of Stat3 and NF-κB signalings. In addition, TAMs rescued the compromised lung metastasis induced by Sox2 silencing in breast cancer cells. Together, this study documented that Sox2 plays an important role in recruiting TAMs and promotes tumor metastasis in a TAMs dependent manner. © 2014 Elsevier Ireland Ltd.

Chen S.,Nankai University | Li X.,Nankai University | Li X.,Beijing Health Vocational College | Lu D.,Nankai University | And 15 more authors.
Carcinogenesis | Year: 2014

Previous studies have implicated cancer stem cells in tumor recurrence and revealed that the stem cell gene SOX2 plays an important role in the tumor cell resistance to apoptosis. Nonetheless, the mechanism by which SOX2 regulates apoptosis signals remained undefined. Here, we demonstrated the surprising finding that silencing of the SOX2 gene effectively induces apoptosis via the activation of death receptor and mitochondrial signaling pathways in human non-small cell lung cancer cells. Unexpectedly, reverse transcription-PCR analysis suggested that downregulation of SOX2 leads to activation of MAP4K4, previously implicated in cell survival. Evaluation of the apoptotic pathways revealed an increased expression of key inducers of apoptosis, including tumor necrosis factor-a and p53, with concurrent attenuation of Survivin. Although p53 appeared dispensable for this pathway, the loss of Survivin in SOX2-deficient cells appeared critical for the observed MAP4K4 induced cell death. Rescue experiments revealed that SOX2-silencing-mediated killing was blocked by ectopic expression of Survivin, or by reduction of MAP4K4 expression. Clinically, expressions of Survivin and SOX2 were highly correlated with each other. The results reveal a key target of SOX2 expression and highlight the unexpected context-dependent role for MAP4K4, a pluripotent activator of several mitogen-activated protein kinase pathways, in regulating tumor cell survival. © The Author 2013. Published by Oxford University Press. All rights reserved.

Wei W.,Nankai University | Li H.,Nankai University | Li N.,Nankai University | Li N.,Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation | And 4 more authors.
Pancreatology | Year: 2013

Background: Expression of WNT5A associated with aggressive tumor biology and poor clinical outcome of various types of cancer. However its function in the metastasis property of pancreatic cells still needs to be elucidated. Methods: We detected the expressions of WNT5A, JNK1/p-JNK1 and Paxillin/p-Paxillin in cancer and the para-carcinoma tissues of pancreatic cancer. To understand how WNT5A/JNK signaling affects pancreatic cancer cell migration through the phosphorylation of cellular substrates of Paxillin, In vitro, we knocked down the WNT5A in PANC1, Capan-2 and HT1080 cell lines, and then tested the expression of JNK1. We detected the proteins of phosphorylation of Paxillin after JNK1 was inhibited and then the cells migration assay was evaluated. Moreover, JNK1 functionally phosphorylates serine178 on paxillin in vitro was detected .At last we subsequently observed whether WNT5A/JNK signaling modulates some molecule expressions relevant to focal adhesion (FA) formation and mesenchymal transition (EMT) and cell cycle. Results: WNT5A, p-JNK1 and p-Paxillin were highly expressed in early stage of tumor tissues. In vitro, WNT5A/JNK signaling promotes cell migration in pancreatic cancer by phosphorylating serine178 on Paxillin, an FA adaptor, which means WNT5A may regulate FA's function.WNT5A up-regulates the molecule's expressions relevant to cell adhesion through the phosphorylation of JNK1, including MMP1, MMP2, ICAM and CD44. In addition, WNT5A/JNK signaling promoted the mRNA expressions of vimentin, but decreased in E-Cadherin expression, which suggested its regulatory effects on the EMT processes. WNT5A/JNK signaling didn't modulate cell proliferation. Conclusion: WNT5A/JNK signaling initiate cell migration of pancreatic cancer through activation of Paxillin, which suggested WNT5A has the potency of being an effective therapeutic target for the metastasis of pancreatic cancer. Copyright © 2013, IAP and EPC.

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