scholarly journals α-Actinin-4 regulates cancer stem cell properties and chemoresistance in cervical cancer

2019 ◽  
Vol 41 (7) ◽  
pp. 940-949 ◽  
Author(s):  
Jaeyeon Jung ◽  
Suhyun Kim ◽  
Hyoung-Tae An ◽  
Jesang Ko
Keyword(s):  
Cervical Cancer ◽  
Cell Cycle Progression ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Cancer Recurrence ◽  
Actin Binding ◽  
Mesenchymal Transition ◽  
Key Factor ◽  
Sphere Formation

Abstract Cancer stem cells (CSCs) initiate tumors and possess the properties of self-renewal and differentiation. Since they are responsible for chemoresistance, CSCs are known to be a key factor in cancer recurrence. α-Actinin-4 (ACTN4) is an actin-binding protein that is involved in muscle differentiation and cancer metastasis. It promotes epithelial to mesenchymal transition and cell cycle progression via β-catenin stabilization in cervical cancer. In the present study, we investigated the role of ACTN4 in regulating cancer cell stemness and chemoresistance in cervical cancer. Results from the gene expression database analysis showed that ACTN4 mRNA expression was elevated in cancerous cervices when compared with normal cervices. Furthermore, ACTN4 knockdown suppressed sphere formation and CSC proliferation. It also decreased CSC size and CD44high/CD24low cell population. ACTN4-knockdown CSCs were sensitive to anticancer drugs, which was observed by down-regulation of the ATP-binding cassette family G2 involved in drug resistance. Finally, ACTN4-knockdown CSCs formed reduced tumors in vivo when compared with control CSCs. Overall, these findings suggest that ACTN4 regulates CSC properties and contributes to chemoresistance in cervical cancer.

scholarly journals MicroRNA in Lung Cancer Metastasis

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 265 ◽  
Author(s):  
Shang-Gin Wu ◽  
Tzu-Hua Chang ◽  
Yi-Nan Liu ◽  
Jin-Yuan Shih
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Cancer Treatments ◽  
Mesenchymal Transition ◽  
Lung Cancer Metastasis ◽  
Targeted Treatments

Tumor metastasis is a hallmark of cancer, with distant metastasis frequently developing in lung cancer, even at initial diagnosis, resulting in poor prognosis and high mortality. However, available biomarkers cannot reliably predict cancer spreading sites. The metastatic cascade involves highly complicated processes including invasion, migration, angiogenesis, and epithelial-to-mesenchymal transition that are tightly controlled by various genetic expression modalities along with interaction between cancer cells and the extracellular matrix. In particular, microRNAs (miRNAs), a group of small non-coding RNAs, can influence the transcriptional and post-transcriptional processes, with dysregulation of miRNA expression contributing to the regulation of cancer metastasis. Nevertheless, although miRNA-targeted therapy is widely studied in vitro and in vivo, this strategy currently affords limited feasibility and a few miRNA-targeted therapies for lung cancer have entered into clinical trials to date. Advances in understanding the molecular mechanism of metastasis will thus provide additional potential targets for lung cancer treatment. This review discusses the current research related to the role of miRNAs in lung cancer invasion and metastasis, with a particular focus on the different metastatic lesions and potential miRNA-targeted treatments for lung cancer with the expectation that further exploration of miRNA-targeted therapy may establish a new spectrum of lung cancer treatments.

scholarly journals CD36 promotes the epithelial–mesenchymal transition and metastasis in cervical cancer by interacting with TGF-β

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Min Deng ◽  
Xiaodong Cai ◽  
Ling Long ◽  
Linying Xie ◽  
Hongmei Ma ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Cd36 Expression ◽  
Cervical Cancer Cells

Abstract Background Accumulating evidence indicates that CD36 initiates metastasis and correlates with an unfavorable prognosis in cancers. However, there are few reports regarding the roles of CD36 in initiation and metastasis of cervical cancer. Methods Using immunohistochemistry, we analyzed 133 cervical cancer samples for CD36 protein expression levels, and then investigated the correlation between changes in its expression and clinicopathologic parameters. The effect of CD36 expression on the epithelial–mesenchymal transition (EMT) in cervical cancer cells was evaluated by Western immunoblotting analysis. In vitro invasion and in vivo metastasis assays were also used to evaluate the role of CD36 in cervical cancer metastasis. Results In the present study, we confirmed that CD36 was highly expressed in cervical cancer samples relative to normal cervical tissues. Moreover, overexpression of CD36 promoted invasiveness and metastasis of cervical cancer cells in vitro and in vivo, while CD36 knockdown suppressed proliferation, migration, and invasiveness. We demonstrated that TGF-β treatment attenuated E-cadherin expression and enhanced the expression levels of CD36, vimentin, slug, snail, and twist in si-SiHa, si-HeLa, and C33a–CD36 cells, suggesting that TGF-β synergized with CD36 on EMT via active CD36 expression. We also observed that the expression levels of TGF-β in si-SiHa cells and si-HeLa cells were down-regulated, whereas the expression levels of TGF-β were up-regulated in C33a–CD36 cells. These results imply that CD36 and TGF-β interact with each other to promote the EMT in cervical cancer. Conclusions Our findings suggest that CD36 is likely to be an effective target for guiding individualized clinical therapy of cervical cancer.

scholarly journals Histone chaperone APLF level dictate implantation of mouse embryo

2020 ◽  
pp. jcs.246900
Author(s):  
Pallavi Chinnu Varghese ◽  
Sruthy Manuraj Rajam ◽  
Debparna Nandy ◽  
Aurelie Jory ◽  
Ananda Mukherjee ◽  
...  
Keyword(s):  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Histone Chaperone ◽  
Breast Cancer Metastasis ◽  
Mouse Development ◽  
Mesenchymal Transition ◽  
Murine Fibroblast ◽  
Post Implantation

Our recent findings demonstrated that histone chaperone and DNA repair factor Aprataxin PNK like factor (APLF) could regulate Epithelial to mesenchymal transition (EMT) during reprogramming of murine fibroblast and in breast cancer metastasis. So, we investigated the function of APLF in EMT associated with mouse development. Here we show that APLF is predominantly enhanced in trophectoderm and lineages derived from trophectoderm in pre and post-implantation embryos. Downregulation of APLF induced hatching of embryos in vitro with a significant increase in Cdh1 and Cdx2 expression. Aplf shRNA microinjected embryos failed to implant in vivo. Rescue experiments neutralized the knockdown effects of APLF both in vitro and in vivo. Reduced expression of Snai2, Tead4 and the gain in Cdh1 and sFlt1 level marked the differentiation of APLF-knocked down Trophoblast Stem Cells that might contribute towards the impaired implantation of embryos. Hence, our findings suggest a novel role of APLF during implantation and post-implantation development of mouse embryos. We anticipate that APLF might contribute to the establishment of maternal-fetal connection, as its fine balance is required to achieve implantation and thereby attain proper pregnancy.

scholarly journals Cofilin: A Promising Protein Implicated in Cancer Metastasis and Apoptosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Jing Xu ◽  
Yan Huang ◽  
Jimeng Zhao ◽  
Luyi Wu ◽  
Qin Qi ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Clinical Treatment ◽  
Actin Binding ◽  
Cytoskeletal Reorganization ◽  
Mesenchymal Transition ◽  
Over Expression ◽  
Actin Binding Protein ◽  
Filament Dynamics

Cofilin is an actin-binding protein that regulates filament dynamics and depolymerization. The over-expression of cofilin is observed in various cancers, cofilin promotes cancer metastasis by regulating cytoskeletal reorganization, lamellipodium formation and epithelial-to-mesenchymal transition. Clinical treatment of cancer regarding cofilin has been explored in aspects of tumor cells apoptosis and cofilin related miRNAs. This review addresses the structure and phosphorylation of cofilin and describes recent findings regarding the function of cofilin in regulating cancer metastasis and apoptosis in tumor cells.

scholarly journals TDO2 Promotes the EMT of Hepatocellular Carcinoma Through Kyn-AhR Pathway

2021 ◽  
Vol 10 ◽  
Author(s):  
Lei Li ◽  
Tao Wang ◽  
Shanbao Li ◽  
Zhengqian Chen ◽  
Junyi Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Aryl Hydrocarbon ◽  
Hcc Cells

Tryptophan 2,3-dioxygenase (TDO2), an enzyme involved in tryptophan (Trp) metabolism has been linked with some malignant traits of various cancers. Kyn, the main product of Trp metabolism pathway catalyzed by TDO2 and indoleamine 2,3-dioxygenase (IDO) in tumor cells, was also demonstrated to activate aryl hydrocarbon receptor (AhR), which may regulate cancer growth and invasion in some malignancies. However, whether TDO2 participates in the metastasis and invasion of HCC has not been explored before. The underlying mechanism played by TDO2 in this process still requires further investigation. Here, we demonstrated that overexpression of TDO2 correlates with advanced stage or malignant traits in HCC patients. Knockdown or inhibition of TDO2 suppressed the migration and invasion of HCC cells in vitro and in vivo. Epithelial to mesenchymal transition (EMT) is an essential program happened in the initial phase of cancer metastasis. We found that in HCC cells, TDO2 promoted the EMT process evidenced by altered levels of biomarkers for EMT. Mechanically, TDO2 regulated the Kyn production in HCC cell via activated aryl hydrocarbon receptor (AhR). Together, these results indicate that TDO2 promotes the EMT of hepatocellular carcinoma through activating Kyn-AhR pathway, thereby participating in the metastasis and invasion of HCC.

scholarly journals Androgen receptor regulates eIF5A2 expression and promotes prostate cancer metastasis via EMT

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yuancai Zheng ◽  
Ping Li ◽  
Hang Huang ◽  
Xueting Ye ◽  
Wei Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Elongation Factor ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Mesenchymal Transition ◽  
Invasion And Migration

AbstractAndrogen receptor (AR) is an androgen-activated transcription factor of the nuclear receptor superfamily. AR plays a role in the development and progression of prostate cancer (PCa). However, the exact role of AR in PCa metastasis remains unclear. In the present study, we aimed to elucidate the function of AR in PCa. We found that eukaryotic translation initiation factor (EIF) 5A2, an elongation factor that induces epithelial-to-mesenchymal transition (EMT) in PCa cells, was significantly upregulated after 5α-dihydrotestosterone (DHT) stimulation and downregulated after anti‐androgen bicalutamide treatment in PCa cells with high AR expression, but not in cells with low AR expression. Moreover, eIF5A2 knockdown could eliminate DHT-induced invasion and migration of AR-positive PCa cells. DHT treatment decreased epithelial expression of E‐cadherin and β-catenin but increased the expression of the mesenchymal marker proteins Vimentin and N-cadherin. DHT therefore induced EMT, and knockdown of eIF5A2 inhibited DHT-induced EMT. Moreover, in vivo study, Luciferase signals from the lungs of the eIF5A2 plasmid group indicated higher metastasis ability, and the eIF5A2 siRNA group had lower metastasis ability. Our results suggest that AR positively regulates eIF5A2 expression in androgen-dependent cells, and stimulation of AR expression and signaling in prostate tumors promotes PCa metastasis by EMT induction and upregulation of eIF5A2.

Circular RNA hsa_circ_0001178 facilitates the invasion and metastasis of colorectal cancer through upregulating ZEB1 via sponging multiple miRNAs

2020 ◽  
Vol 401 (4) ◽  
pp. 487-496 ◽  
Author(s):  
Chunfeng Ren ◽  
Zhenmin Zhang ◽  
Shunhua Wang ◽  
Weitao Zhu ◽  
Peiguo Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Underlying Mechanism ◽  
Circular Rna ◽  
Mechanistic Study ◽  
Mesenchymal Transition ◽  
Promising Treatment

AbstractMetastasis is the main cause of increasing cancer morbidity and mortality. However, the underlying mechanism of cancer metastasis remains largely unknown. In the present study, we identified one circular RNA (circRNA) closely related to the metastasis of colorectal cancer (CRC), namely hsa_circ_0001178. CRC patients with high hsa_circ_0001178 were more prone to have metastatic clinical features, advanced TNM stage and adverse prognosis. Stable knockdown of hsa_circ_0001178 significantly weakened CRC cell migratory and invasive capabilities in vitro as well as lung and liver metastases in vivo. Mechanistic study revealed that hsa_circ_0001178 acted as a competing endogenous RNA (ceRNA) for miR-382/587/616 to upregulate ZEB1 (a key trigger of epithelial-to-mesenchymal transition), thereby promoting CRC metastatic dissemination. Of note, ZEB1 could also increase hsa_circ_0001178 expression via physically binding to hsa_circ_0001178 promoter region. Collectively, our data uncover the crucial role of hsa_circ_0001178 in CRC metastasis, and targeted therapy based on this positive feedback ceRNA axis may be a promising treatment for metastatic CRC patients.

scholarly journals Knockdown of RhoE Expression Enhances TGF-β-Induced EMT (epithelial-to-mesenchymal transition) in Cervical Cancer HeLa Cells

2019 ◽  
Vol 20 (19) ◽  
pp. 4697 ◽  
Author(s):  
Makoto Nishizuka ◽  
Rina Komada ◽  
Masayoshi Imagawa
Keyword(s):  
Cervical Cancer ◽  
Hela Cells ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Negative Regulator ◽  
Surrounding Tissue ◽  
Rock Inhibitor ◽  
Mesenchymal Transition

Cervical cancer with early metastasis of the primary tumor is associated with poor prognosis and poor therapeutic outcomes. Since epithelial-to-mesenchymal transition (EMT) plays a role in acquisition of the ability to invade the pelvic lymph nodes and surrounding tissue, it is important to clarify the molecular mechanism underlying EMT in cervical cancer. RhoE, also known as Rnd3, is a member of the Rnd subfamily of Rho GTPases. While previous reports have suggested that RhoE may act as either a positive or a negative regulator of cancer metastasis and EMT, the role of RhoE during EMT in cervical cancer cells remains unclear. The present study revealed that RhoE expression was upregulated during transforming growth factor-β (TGF-β)-mediated EMT in human cervical cancer HeLa cells. Furthermore, reduced RhoE expression enhanced TGF-β-mediated EMT and migration of HeLa cells. In addition, we demonstrated that RhoE knockdown elevated RhoA activity and a ROCK inhibitor partially suppressed the acceleration of TGF-β-mediated EMT by RhoE knockdown. These results indicate that RhoE suppresses TGF-β-mediated EMT, partially via RhoA/ROCK signaling in cervical cancer HeLa cells.

scholarly journals GATA3 recruits UTX for gene transcriptional activation to suppress metastasis of breast cancer

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Wenqian Yu ◽  
Wei Huang ◽  
Yang Yang ◽  
Rongfang Qiu ◽  
Yi Zeng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcriptional Activation ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Breast Cancer Metastasis ◽  
Mesenchymal Transition ◽  
Gata3 Expression ◽  
Histone H3k27

Abstract GATA3 has emerged as a prominent transcription factor required for maintaining mammary-gland homeostasis. GATA3 loss is associated with aggressive breast cancer development, but the mechanism by which breast cancer is affected by the loss of GATA3 function remains unclear. Here, we report that GATA3 expression is positively correlated with the expression of UTX, a histone H3K27 demethylase contained in the MLL4 methyltransferase complex, and that GATA3 recruits the chromatin-remodeling MLL4 complex and interacts directly with UTX, ASH2L, and RBBP5. Using RNA sequencing and chromatin immunoprecipitation and sequencing, we demonstrate that the GATA3/UTX complex synergistically regulates a cohort of genes including Dicer and UTX, which are critically involved in the epithelial-to-mesenchymal transition (EMT). Our results further show that the GATA3-UTX-Dicer axis inhibits EMT, invasion, and metastasis of breast cancer cells in vitro and the dissemination of breast cancer in vivo. Our study implicates the GATA3-UTX-Dicer axis in breast cancer metastasis and provides new mechanistic insights into the pathophysiological function of GATA3.

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