scholarly journals Ferritinophagic Flux Was a Driving Force in Determination of Status of EMT, Ferroptosis, and NDRG1 Activation in Action of Mechanism of 2-Pyridylhydrazone Dithiocarbamate S-Acetic Acid

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Hao Li ◽  
Wei Zhou ◽  
Huiping Wei ◽  
Longlong Li ◽  
Xu Wang ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Driving Force ◽  
Epithelial Mesenchymal Transition ◽  
Ros Production ◽  
Regulatory Effect ◽  
Mesenchymal Transition ◽  
Cellular Events ◽  
The Status ◽  
Related Proteins

Ferritinophagy is a process of ferritin degradation in lysosomes; however, how its effect on other cellular events, such as epithelial-mesenchymal transition (EMT) and ferroptosis remains elusive. In this study, we determined how ferritinophagic flux influence the status of EMT and ferroptosis in HepG2 cell. Our data revealed that 2-pyridylhydrazone dithiocarbamate s-acetic acid (PdtaA) induced EMT inhibition involved ferritinophagy-mediated ROS production, but addition of ferrostatin-1 could attenuate the effect of PdtaA on the regulation of EMT-related proteins, suggesting that ferroptosis might involve in the EMT regulation. Next, downregulation of Gpx4 and xCT as well as enhanced lipid peroxidation further supported that PdtaA was able to induce ferroptosis. Knockdown of NCOA4 significantly attenuated the regulatory effect of PdtaA on related proteins which highlighted that the strength of ferritinophagic flux (NCOA4/ferritin) was a driving force in determination of the status of EMT and ferroptosis. Furthermore, NDRG1 activation was also observed, and knockdown of NDRG1 similarly influenced the expressions of ferroptosis-related proteins, suggesting that NDRG1 also involved ferroptosis induction, which was first reported. Taken together, PdtaA-induced EMT inhibition, ferroptosis, and NDRG1 activation all depended on the strength of ferritinophagic flux.

scholarly journals Ferritinophagic Flux Activation in CT26 Cells Contributed to EMT Inhibition Induced by a Novel Iron Chelator, DpdtpA

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Yanjie Sun ◽  
Cuiping Li ◽  
Jiankang Feng ◽  
Yongli Li ◽  
Xinbo Zhai ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Correlation Analysis ◽  
Driving Force ◽  
Epithelial Mesenchymal Transition ◽  
Iron Chelator ◽  
Iron Chelators ◽  
Ros Production ◽  
Mesenchymal Transition ◽  
New Finding ◽  
The Relationship

Epithelial-mesenchymal transition (EMT) contributes to metastasis and drug resistance; inhibition of EMT may attenuate metastasis and drug resistance. It has been demonstrated that ferritinophagy involves the process of many diseases; however, the relationship between EMT and ferritinophagy was not fully established. Some iron chelators show the ability to inhibit EMT, but whether ferritinophagy plays a role in EMT is largely unknown. To this end, we investigated the effect of a novel iron chelator, DpdtpA (2,2′-di-pyridylketone dithiocarbamate propionic acid), on EMT in the CT26 cell line. The DpdtpA displayed excellent antitumor (IC50=1.5±0.2 μM), leading to ROS production and apoptosis occurrence. Moreover, the ROS production correlated with ferritin degradation. The upregulation of LC3-II and NCOA4 from immunofluorescence and Western blotting analysis revealed that the occurrence of ferritinophagy contributed to ROS production. Furthermore, DpdtpA could induce an alteration both in morphology and in epithelial-mesenchymal markers, displaying significant EMT inhibition. The correlation analysis revealed that DpdtpA-induced ferritinophagy contributed to the EMT inhibition, implying that NCOA4 involved EMT process, which was firstly reported. To reinforce this concept, the ferritinophagic flux (NCOA4/ferritin) in either treated by TGF-β1 or combined with DpdtpA was determined. The results indicated that activating ferritinophagic flux would enhance ROS production which accordingly suppressed EMT or implementing the EMT suppression seemed to be through “fighting fire with fire” strategy. Taken together, our data demonstrated that ferritinophagic flux was a dominating driving force in EMT proceeding, and the new finding definitely will enrich our knowledge of ferritinophagy in EMT process.

scholarly journals CHN1 promotes epithelial–mesenchymal transition via the Akt/GSK-3β/Snail pathway in cervical carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Haoqi Zhao ◽  
Lan Wang ◽  
Shufang Wang ◽  
Xihua Chen ◽  
Min Liang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lymph Node ◽  
Signaling Pathway ◽  
Cervical Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Xenograft Tumor ◽  
Mesenchymal Transition ◽  
Gsk 3Β ◽  
Related Proteins

Abstract Background Metastasis and invasion are crucial in determining the mortality of cervical carcinoma (CC) patients. The epithelial–mesenchymal transition (EMT) is now a universal explanation for the mechanisms of tumor metastasis. Α-chimeric protein (α-chimaerin, CHN1) plays an important role in the regulation of signal transduction and development. However, the molecular regulatory relationships between CHN1 and CC progression in relation to EMT have not yet been identified. Methods The expression of CHN1 in CC tissues, adjacent tissues, and lymph node metastases from CC patients was detected by immunohistochemistry. Upregulation and knockdown of CHN1 were achieved by transfection of CC cells. The effect of CHN1 on cell proliferation was determined by CCK-8 and plate clone formation assays. Changes in migration and invasion capabilities were evaluated using scratch migration and transwell invasion assays. The effect of CHN1 overexpression and interference on xenograft tumor growth was determined by tumor weight and pathological analyses. The expression of EMT-related mRNAs was measured by qRT-PCR in transfected CC cells. EMT-related proteins and Akt/GSK-3β/Snail signaling pathway-related proteins were also evaluated by western blotting. Results CHN1 was overexpressed in CC tissues and was associated with lymph node metastasis and low survival in CC patients. Overexpression of CHN1 promoted cell proliferation, migration, and invasion in CC cells. In contrast, silencing of CHN1 inhibited these phenomena. Overexpression of CHN1 promoted tumor formation in an in vivo xenograft tumor mouse model, with increased tumor volumes and weights. In addition, CHN1 induced the expression of EMT-related transcription factors, accompanied by the decreased expression of epithelial markers and increased expression of mesenchymal markers. The Akt/GSK-3β/Snail signaling pathway was activated by overexpression of CHN1 in vitro, and activation of this pathway was inhibited by the signaling pathway inhibitor LY294002. Conclusion These results suggest that CHN1 promotes the development and progression of cervical carcinoma via the Akt/GSK-3β/Snail pathway by inducing EMT.

scholarly journals The Role of microRNAs in Cholangiocarcinoma

2021 ◽  
Vol 22 (14) ◽  
pp. 7627
Author(s):  
Tingting Shi ◽  
Asahiro Morishita ◽  
Hideki Kobara ◽  
Tsutomu Masaki
Keyword(s):  
Cell Cycle Progression ◽  
Target Genes ◽  
Epithelial Mesenchymal Transition ◽  
Survival Rates ◽  
Therapy Resistance ◽  
Resistance Mechanisms ◽  
Mesenchymal Transition ◽  
Diagnosis And Prognosis ◽  
Related Risk

Cholangiocarcinoma (CCA), an aggressive malignancy, is typically diagnosed at an advanced stage. It is associated with dismal 5-year postoperative survival rates, generating an urgent need for prognostic and diagnostic biomarkers. MicroRNAs (miRNAs) are a class of non-coding RNAs that are associated with cancer regulation, including modulation of cell cycle progression, apoptosis, metastasis, angiogenesis, autophagy, therapy resistance, and epithelial–mesenchymal transition. Several miRNAs have been found to be dysregulated in CCA and are associated with CCA-related risk factors. Accumulating studies have indicated that the expression of altered miRNAs could act as oncogenic or suppressor miRNAs in the development and progression of CCA and contribute to clinical diagnosis and prognosis prediction as potential biomarkers. Furthermore, miRNAs and their target genes also contribute to targeted therapy development and aid in the determination of drug resistance mechanisms. This review aims to summarize the roles of miRNAs in the pathogenesis of CCA, their potential use as biomarkers of diagnosis and prognosis, and their utilization as novel therapeutic targets in CCA.

scholarly journals Epithelial–mesenchymal transition and metastasis of colon cancer cells induced by the FAK pathway in cancer-associated fibroblasts

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052093124
Author(s):  
Xuefeng Xuefeng ◽  
Ming-Xing Hou ◽  
Zhi-Wen Yang ◽  
Agudamu Agudamu ◽  
Feng Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
3D Culture ◽  
Cancer Associated Fibroblasts ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
Lovo Cells ◽  
Related Proteins

Objective The role and mechanism of tetrathiomolybdate (TM) in cancer-associated fibroblasts (CAFs) in colon cancer using three-dimensional (3D) culture were investigated, and the associations between the focal adhesion kinase (FAK) pathway and epithelial–mesenchymal transition (EMT) in CAFs were explored. Methods A 3D co-culture model of colon cancer LOVO cells with CAFs and normal fibroblasts (NFs) was established using Matrigel as a scaffold material. The differential expression of LOXL2 (lysyl oxidase-like 2) in the supernatant of CAFs and NFs was determined using ELISA, and expression levels of EMT-related proteins and FAK signaling pathway-related proteins were determined using western blot. Results LOXL2 levels secreted by CAFs were higher compared with that secreted by NFs. In the CAF + LOVO group, compared with the LOVO group, E-cadherin expression decreased significantly, while N-cadherin and F-PAK expression increased significantly. TM results were opposite compared with the above results. Conclusions CAFs stimulate EMT in human colon cancer LOVO cells by secreting LOXL2 to activate the FAK signaling pathway, thereby promoting tumor metastasis. TM inhibited the occurrence of EMT in the CAF-induced colon cancer LOVO cell line, thereby reducing the invasion and metastasis of colon cancer cells.

scholarly journals Role of HOXC10 in Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jinyong Fang ◽  
Jianjun Wang ◽  
Liangliang Yu ◽  
Wenxia Xu
Keyword(s):  
Hox Genes ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Limb Regeneration ◽  
Morphological Development ◽  
Mesenchymal Transition ◽  
Oncogenic Pathways ◽  
The Status ◽  
Sex Regulation

The HOXC10 gene, a member of the HOX genes family, plays crucial roles in mammalian physiological processes, such as limb morphological development, limb regeneration, and lumbar motor neuron differentiation. HOXC10 is also associated with angiogenesis, fat metabolism, and sex regulation. Additional evidence suggests that HOXC10 dysregulation is closely associated with various tumors. HOXC10 is an important transcription factor that can activate several oncogenic pathways by regulating various target molecules such as ERK, AKT, p65, and epithelial mesenchymal transition-related genes. HOXC10 also induces drug resistance in cancers by promoting the DNA repair pathway. In this review, we summarize HOXC10 gene structure and expression as well as the role of HOXC10 in different human cancer processes. This review will provide insight into the status of HOXC10 research and help identify novel targets for cancer therapy.

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