Id-2 regulates critical aspects of human cytotrophoblast differentiation, invasion and migration

Development ◽  
2000 ◽  
Vol 127 (3) ◽  
pp. 549-558 ◽  
Author(s):  
M.J. Janatpour ◽  
M.T. McMaster ◽  
O. Genbacev ◽  
Y. Zhou ◽  
J. Dong ◽  
...  
Keyword(s):  
Dna Binding ◽  
Adenovirus Vector ◽  
Bhlh Transcription Factor ◽  
Placental Development ◽  
Invasion And Migration ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Bhlh Factors ◽  
Cytotrophoblast Cells ◽  
And Migration

During early human placental development, the conceptus attaches itself to the uterus through cytotrophoblast invasion. Invasive cytotrophoblast cells differentiate from precursor villous cytotrophoblasts, but the essential regulating factors in this process are unknown. Basic helix-loop-helix (bHLH) transcription factor dimers are essential regulators of mouse trophoblast development. We therefore examined the importance of this family of factors in the human placenta. In many cell lineages, bHLH factors are sequestered by members of the Id family, HLH proteins that lack the basic DNA binding domain (Inhibitor of DNA binding proteins (Id-1 to Id-4)). During differentiation of some tissues, Id expression declines, allowing bHLH factors to dimerize, bind DNA and trans-activate lineage-specific genes. To begin to study the role of bHLH transcription factors in human placental development, we first characterized Id expression in cytotrophoblast cells. The cells expressed Id-3 constitutively; Id-2 was downregulated, at the mRNA and protein levels, as the cells differentiated in culture and in situ, respectively. In cases when cytotrophoblast differentiation was compromised (in placentas from women with preeclampsia, or in cells grown under hypoxic conditions in culture), Id-2 expression was maintained. To assess the functional relevance of these correlations, we used an adenovirus vector to maintain Id-2 protein expression in cultured cytotrophoblasts. Compared to control (lacZ-expressing) cells, cytotrophoblasts transduced to constitutively express Id-2 retained characteristics of undifferentiated cells: (alpha)1 integrin expression was low and cyclin B expression was retained. Furthermore, invasion through Matrigel was partially inhibited and migration was strikingly enhanced in Id-2-expressing cells. These results suggest that Id-2 and the bHLH factors that it partners play important roles in human cytotrophoblast development.

scholarly journals LncRNA MCM3AP-AS1 sponges miR-148a to enhance cell invasion and migration in small cell lung cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hua Luo ◽  
Yukun Zhang ◽  
Guangmei Qin ◽  
Bing Jiang ◽  
Lili Miao
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cell Invasion ◽  
Small Cell ◽  
Small Cell Lung ◽  
Invasion And Migration ◽  
Protein Levels ◽  
Underlying Mechanisms ◽  
And Migration

Abstract Background MCM3AP-AS1 is a recently characterized lncRNA playing an oncogenic role in several cancers. However, its role in lung cancer remains unknown. Here, we aimed to explore the functions of MCM3AP-AS1 in small cell lung cancer (SCLC) and the possible underlying mechanisms. Methods MCM3AP-AS1 and ROCK1 levels in SCLC patients were analyzed by qPCR. RNA pull-down and luciferase assays were performed to analyze the interaction between MCM3AP-AS1 and miR-148a. ROCK1 mRNA and protein levels were detected by qPCR and Western blot, respectively. Cell invasion and migration were analyzed by Transwell assays. Results MCM3AP-AS1 was upregulated in patients with SCLC, and a high MCM3AP-AS1 level was accompanied by a low survival rate. The binding of MCM3AP-AS1 to miR-148a predicted by bioinformatics analysis was verified by RNA pull-down and luciferase assays. However, MCM3AP-AS1 and miR-148a did not affect each other’s expression. ROCK1 was upregulated in SCLC tissues and positively correlated with MCM3AP-AS1. In SCLC cells, MCM3AP-AS1 overexpression increased ROCK1 and promoted cancer cell invasion and migration, while miR-148a overexpression showed the opposite effects and attenuated the effects of MCM3AP-AS1 overexpression on ROCK1 expression and cell behaviors. Conclusions MCM3AP-AS1 sponges miR-148a, thereby increasing SCLC cell invasion and migration via upregulating ROCK1 expression.

ERK5 and its role in tumour development

2012 ◽  
Vol 40 (1) ◽  
pp. 251-256 ◽  
Author(s):  
Pamela A. Lochhead ◽  
Rebecca Gilley ◽  
Simon J. Cook
Keyword(s):  
Mitogen Activated Protein Kinase ◽  
Invasion And Migration ◽  
Extracellular Signal Regulated Kinase ◽  
Protein Levels ◽  
Extracellular Signal ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Tumour Cell Invasion ◽  
And Migration

The MEK5 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 5]/ERK5 pathway is the least well studied MAPK signalling module. It has been proposed to play a role in the pathology of cancer. In the present paper, we review the role of the MEK5/ERK5 pathway using the ‘hallmarks of cancer’ as a framework and consider how this pathway is deregulated. As well as playing a key role in endothelial cell survival and tubular morphogenesis during tumour neovascularization, ERK5 is also emerging as a regulator of tumour cell invasion and migration. Several oncogenes can stimulate ERK5 activity, and protein levels are increased by a novel amplification at chromosome locus 17p11 and by down-regulation of the microRNAs miR-143 and miR-145. Together, these finding underscore the case for further investigation into understanding the role of ERK5 in cancer.

scholarly journals Annexin A2 Coordinates STAT3 to Regulate the Invasion and Migration of Colorectal Cancer CellsIn Vitro

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Dianhui Xiu ◽  
Lin Liu ◽  
Fengli Qiao ◽  
Haishan Yang ◽  
Lu Cui ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Annexin A2 ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Protein Levels ◽  
And Migration

The present study aimed to reveal the expression of STAT3 and Anxa 2 in CRC specimens and to investigate the effects of STAT3 and Anxa 2 signaling on the proliferation, invasion, and migration in CRC Caco-2 cells. Results demonstrated that both Anxa 2 and STAT3 were highly expressed in CRC specimens in both mRNA and protein levels, with or without phosphorylation (Tyrosine 23 in Anxa 2 and Tyrosine 705 in STAT3). And the upregulated Anxa 2 promoted the phosphorylation of STAT3 (Tyrosine 705) in CRC Caco-2 cells. The upregulated Anxa 2 promoted the proliferation, migration, and invasion of Caco-2 cells in vitro. Moreover, the STAT3 knockdown also repressed the proliferation, migration, and invasion of Caco-2 cells. In conclusion, the overexpressed Annexin A2 regulated the proliferation, invasion, and migration in CRC cells in an association with STAT3.

Knockdown of TPPP3 to inhibit cell proliferation and invasion in human colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23006-e23006 ◽  
Author(s):  
Yintao Li ◽  
Jinming Yu
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Protein Family ◽  
Migration And Invasion ◽  
Clinicopathologic Characteristics ◽  
Invasion And Migration ◽  
Protein Levels ◽  
Angiogenesis Assay ◽  
And Migration

e23006 Background: Tubulin Polymerization Promoting Protein Family Member 3, TPPP3, a member of the TPPP protein family, has been reported to play important roles in initiation and progression of human cancers, such as lung cancer. However, the expression and underlying function of TPPP3 in colorectal cancer (CRC) have not yet been fully clarified. Methods: In this study, the mRNA and protein levels of TPPP3 in 96 clinical CRC specimens were determined by RT-PCR and immunohistochemistry. The relation between TPPP3 expression and clinicopathologic characteristics and overall survival (OS) were evaluated. TPPP3 was stably knockdowned by shRNA. In addition, CCK-8、Colony formation、Flow cytometric、Transwell and Angiogenesis assay were to examine the biological function of TPPP3 in CRC cells in vitro. Results: We show that TPPP3 was significantly increased in CRC tissues and associated with aggressive factors and poor patient survival. Further experiments showed that knockdown of TPPP3 inhibited cell proliferation, migration and invasion and induced cell apoptosis in vitro. In addition, TPPP3 silencing resulted in a decrease of angiogenesis and S phase fraction. And TPPP3 significantly affected the invasion and migration of CRC cells via the expression of MMP-9, Rac-1 and E-cadherin. Conclusions: Our results suggested that TPPP3 played an important role in CRC progress and might serve as novel therapeutic targets for CRC treatment.

scholarly journals Hsa_circ_002178 Promotes the Growth and Migration of Breast Cancer Cells and Maintains Cancer Stem-like Cell Properties Through Regulating miR-1258/KDM7A Axis

2020 ◽  
Vol 29 ◽  
pp. 096368972096017
Author(s):  
Wangyong Li ◽  
Xiaoyan Yang ◽  
Chengfei Shi ◽  
Zhengbo Zhou
Keyword(s):  
Breast Cancer ◽  
Inhibitory Effect ◽  
Invasion And Migration ◽  
Protein Levels ◽  
Elevated Protein ◽  
Underlying Mechanisms ◽  
And Migration ◽  
Cancer Tissues ◽  
Increased Activity ◽  
Common Malignancy

Breast cancer (BrCa) is the most common malignancy in women. Accumulating evidence demonstrated that abnormal circRNA expression is associated with the occurrence and progression of tumors. We analyzed the GSE101123 data and found that the expression of hsa_circ_002178 (circ_002178) was significantly increased in BrCa tissues. However, the role and possible underlying mechanisms of circ_002178 in BrCa still remain unrevealed. In this investigation, the expression levels of circ_002178 in cancer tissues or BrCa cells were significantly upregulated compared with those in paracancer tissues or normal cells. High expression of circ_002178 was correlated with the low survival rate, clinical tumor size, lymph node metastasis, and tumor, nodes, and metastases grade. After microsphere culture, the expression of circ_002178 in SUM149PT and MDA-MB-231 cells was significantly increased. Further investigation exhibited that overexpression of circ_002178 contributed to the formation of microspheres, the elevated protein levels of stemness marker, and the increased activity of ALDH1 in SUM149PT cells. Besides, the overexpression of circ_002178 also significantly promoted the growth, invasion, and migration of BrCa cells. Correspondingly, the knockdown of circ_002178 showed the opposite result in MDA-MB-231 cells. Hsa_circ_002178 was further proved to downregulate the level of miR-1258 and reduce the inhibitory effect of miR-1258 on KDM7A, thus regulating the stem-like characteristics of BrCa cells and promoting the growth and migration of BrCa cells. Taken together, targeting the circ_002178/miR-1258/KDM7A axis may be a prospective strategy for the diagnosis and therapies of BrCa in the future.

Interleukin 11: similar or opposite roles in female reproduction and reproductive cancer?

2016 ◽  
Vol 28 (4) ◽  
pp. 395 ◽  
Author(s):  
Amy Winship ◽  
Ellen Menkhorst ◽  
Michelle Van Sinderen ◽  
Evdokia Dimitriadis
Keyword(s):  
Embryo Implantation ◽  
Cell Types ◽  
Malignant Cell ◽  
Vascular Supply ◽  
Female Reproduction ◽  
Placental Development ◽  
Invasion And Migration ◽  
Gynaecological Malignancy ◽  
Uterine Environment ◽  
And Migration

During placental development and carcinogenesis, cell invasion and migration are critical events in establishing a self-supporting vascular supply. Interleukin (IL)-11 is a pleiotropic cytokine that affects the invasive and migratory capabilities of trophoblast cells that form the placenta during pregnancy, as well as various malignant cell types. The endometrium is the site of embryo implantation during pregnancy; conversely, endometrial carcinoma is the most common gynaecological malignancy. Here, we review what is known about the role of IL-11 in trophoblast function and in gynaecological malignancies, focusing primarily on the context of the uterine environment.

Downregulation of aromatase plays a dual role in preeclampsia

2021 ◽  
Author(s):  
Dawei Zhu ◽  
Jie Huang ◽  
Xing Gu ◽  
Li Li ◽  
Jian Han
Keyword(s):  
Infant Health ◽  
Animal Experiments ◽  
Dual Role ◽  
Main Role ◽  
Placental Development ◽  
Serum Samples ◽  
Invasion And Migration ◽  
Maternal And Infant Health ◽  
Pregnant Mice ◽  
And Migration

Abstract Preeclampsia (PE) is a gestational disease which seriously impairs maternal and infant health. However, the pathogenesis of PE remains unclear. The aromatase (CYP19A1) in placenta converts androgens from maternal and fetal adrenal glands to estrogen. Therefore, this change in the aromatase expression or function and the subsequent change of steroids in the placenta could be related to the pathophysiology of PE. In this study, we first analysed the expression of CYP19A1 in clinical placental tissues as well as the level of sex hormones in corresponding serum samples. The results showed that the expression of aromatase in the placenta of PE patients was relatively low and accompanied by a sex hormone imbalance. Subsequently, animal experiments showed that ischemia and hypoxia lead to a low expression of CYP19A1, and that PE-like symptoms appear in pregnant mice following decreased or inhibited CYP19A1 expression. It was also found that, with the downregulation of CYP19A1 expression, the invasion and migration abilities of trophoblast cells were enhanced, which benefited placental implantation. However, alongside this, apoptosis and the inflammatory response were also increased, which was detrimental to placental development. Phosphoproteomic analyses revealed that the activation of the PI3K/AKT signaling pathway may play a key role in these processes. In conclusion, the downregulation of aromatase has a dual role in PE, among which the induction of the disease is the main role. Our study provides a potential novel method for the early prediction and treatment of PE.

scholarly journals Amygdalin promotes the activity of T cells to suppress the progression of HBV-related hepatocellular carcinoma via the JAK2/STAT3 signaling pathway

2019 ◽  
Author(s):  
Ruoyu Wang ◽  
Dong Zhang ◽  
Kewei Sun ◽  
Jianping Peng ◽  
Wenfang Zhu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cell Viability ◽  
Invasion And Migration ◽  
Protein Levels ◽  
Ifn Γ ◽  
And Migration ◽  
Cellular Immune

Abstract Purpose Hepatitis B virus (HBV) infection is a high-risk factor of hepatocellular carcinoma (HCC). Cellular immune responses are essential for HCC development, and the CD4+ and CD8+ T subtypes are identified as the primary anti-tumor immune cells. In the study, we investigated the effect and mechanism of amygdalin in the cellular immune response in HBV-related HCC and HCC progression.Methods The cell proliferation was examined by MTT analysis. Cells metastasis ability was detected by Invasion and migration assays. Quantification of apoptotic cells was performed with Flow cytometer assay. The protein levels of p-STAT3, STAT3, p-JAK2, and JAK2 were detected by performing immunoblotting assays.Results We demonstrate that amygdalin treatment could rescue the HBV-T cell viability and IFN-γ and TNF-αproduction. In HBV-T cells, the MFI levels of CD8+ are lower than that in NC-T cells. Moreover, the phosphorylation levels of STAT3 and JAK2 are higher in HBV-T cells, compared to those in NC-T cells, and then reduced by amygdalin treatment. Co-culture with HBV-T cells could reduce IFN-γ and TNF-α, production while increase IL-6 and IL-10 production in HepG2.2.15 cells; these alterations could be partially reversed by amygdalin pretreatment. Finally, co-culture with HBV-T cells significantly promoted the cell viability, inhibited the apoptosis, and promoted the migration of HepG2.2.15 cells, and these alterations could be partially reversed by amygdalin treatment.Conclusion Our findings provide a rationale for further studies on the functions and mechanism of amygdalin inhibiting HBV-related HCC cell proliferation, invasion, and migration via T cell-mediated tumor immunity.

scholarly journals Homeobox B2 is a potential prognostic biomarker of glioblastoma

2020 ◽  
Vol 66 (6) ◽  
pp. 794-799
Author(s):  
Ming Li ◽  
Jiu-Fei Wang ◽  
Bo Liu ◽  
Xiao-Min Wang
Keyword(s):  
Cell Lines ◽  
Western Blotting ◽  
Prognostic Indicator ◽  
Vital Role ◽  
Invasion And Migration ◽  
Protein Levels ◽  
Promising Target ◽  
Associated Proteins ◽  
Mrna And Protein Expression ◽  
And Migration

SUMMARY OBJECTIVES HOXB2 is a new prognostic indicator for lung cancer. But it is unclear whether HOXB2 holds an effect in glioblastoma (GBM) progression. The purpose of this article was to probe the influences of HOXB2 on GBM pathogenesis. METHODS HOXB2 expression level and prognostic power in GBM patients were analyzed. Then the mRNA and protein expression levels of HOXB2 in GBM cell lines were tested by qRT-PCR and western blotting. Cell proliferation, invasion, and migration were determined by CCK8 and transwell assay, severally. The protein levels of PI3K/AKT-pathway associated proteins were analyzed by western blotting. RESULTS The results indicated that HOXB2 was distinctly overexpressed in GBM patients and high expression of HOXB2 was related to a poor prognosis. Moreover, the expression of HOXB2 was higher in all GBM cell lines U251, U-87MG, GOS-3 than that in HEB cells (normal control). Meanwhile, decreased expression of p-PI3K and p-AKT were identified after HOXB2 knockdown. CONCLUSIONS These data demonstrated that HOXB2 had a vital role in GBM progression and could serve as a promising target for GBM treatment.

Sign in / Sign up

Export Citation Format

Share Document