Multifunctional Role of Astrocyte Elevated Gene-1 (AEG-1) in Cancer: Focus on Drug Resistance

Cancer development results from the acquisition of numerous genetic and epigenetic alterations in cancer cells themselves, as well as continuous changes in their microenvironment. The plasticity of cancer cells allows them to continuously adapt to selective pressures brought forth by exogenous environmental stresses, the internal milieu of the tumor and cancer treatment itself. Resistance to treatment, either inherent or acquired after the commencement of treatment, is a major obstacle an oncologist confronts in an endeavor to efficiently manage the disease. Resistance to chemotherapy, chemoresistance, is an important hallmark of aggressive cancers, and driver oncogene-induced signaling pathways and molecular abnormalities create the platform for chemoresistance. The oncogene Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) is overexpressed in a diverse array of cancers, and its overexpression promotes all the hallmarks of cancer, such as proliferation, invasion, metastasis, angiogenesis and chemoresistance. The present review provides a comprehensive description of the molecular mechanism by which AEG-1 promotes tumorigenesis, with a special emphasis on its ability to regulate chemoresistance.

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Emodin Enhances the Chemosensitivity of Endometrial Cancer by Inhibiting ROS-Mediated Cisplatin-resistance

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666171219113036 ◽

2018 ◽

Vol 18 (7) ◽

pp. 1054-1063 ◽

Cited By ~ 4

Author(s):

Ning Ding ◽

Hong Zhang ◽

Shan Su ◽

Yumei Ding ◽

Xiaohui Yu ◽

...

Keyword(s):

Drug Resistance ◽

Endometrial Cancer ◽

Cancer Cells ◽

Chemotherapeutic Agent ◽

Annexin V ◽

Chemotherapeutic Agents ◽

Endometrial Cancer Cell ◽

Animal Survival ◽

Apoptosis Level

Background: Endometrial cancer is a common cause of death in gynecological malignancies. Cisplatin is a clinically chemotherapeutic agent. However, drug-resistance is the primary cause of treatment failure. Objective: Emodin is commonly used clinically to increase the sensitivity of chemotherapeutic agents, yet whether Emodin promotes the role of Cisplatin in the treatment of endometrial cancer has not been studied. Method: CCK-8 kit was utilized to determine the growth of two endometrial cancer cell lines, Ishikawa and HEC-IB. The apoptosis level of Ishikawa and HEC-IB cells was detected by Annexin V / propidium iodide double-staining assay. ROS level was detected by DCFH-DA and NADPH oxidase expression. Expressions of drug-resistant genes were examined by real-time PCR and Western blotting. Results: Emodin combined with Cisplatin reduced cell growth and increased the apoptosis of endometrial cancer cells. Co-treatment of Emodin and Cisplatin increased chemosensitivity by inhibiting the expression of drugresistant genes through reducing the ROS levels in endometrial cancer cells. In an endometrial cancer xenograft murine model, the tumor size was reduced and animal survival time was increased by co-treatment of Emodin and Cisplatin. Conclusion: This study demonstrates that Emodin enhances the chemosensitivity of Cisplatin on endometrial cancer by inhibiting ROS-mediated expression of drug-resistance genes.

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Emerging roles of cancer-testis antigenes, semenogelin 1 and 2, in neoplastic cells

Cell Death Discovery ◽

10.1038/s41420-021-00482-4 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Oleg Shuvalov ◽

Alyona Kizenko ◽

Alexey Petukhov ◽

Olga Fedorova ◽

Alexandra Daks ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Tumor Cells ◽

Reproductive System ◽

Seminal Fluid ◽

Cancer Development ◽

Migration And Invasion ◽

Malignant Cells ◽

Cancer Testis

AbstractCancer-testicular Antigens (CTAs) belong to a group of proteins that under normal conditions are strictly expressed in a male’s reproductive tissues. However, upon malignisation, they are frequently re-expressed in neoplastic tissues of various origin. A number of studies have shown that different CTAs affect growth, migration and invasion of tumor cells and favor cancer development and metastasis. Two members of the CTA group, Semenogelin 1 and 2 (SEMG1 and SEMG2, or SEMGs) represent the major component of human seminal fluid. They regulate the motility and capacitation of sperm. They are often re-expressed in different malignancies including breast cancer. However, there is almost no information about the functional properties of SEMGs in cancer cells. In this review, we highlight the role of SEMGs in the reproductive system and also summarize the data on their expression and functions in malignant cells of various origins.

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Polo-Like Kinase 4’s Critical Role in Cancer Development and Strategies for Plk4-Targeted Therapy

Frontiers in Oncology ◽

10.3389/fonc.2021.587554 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiaoyang Zhang ◽

Cheng Wei ◽

Hao Liang ◽

Lei Han

Keyword(s):

Cell Cycle ◽

Cancer Diagnosis ◽

Molecular Level ◽

Critical Role ◽

Cancer Development ◽

Tumor Biomarker ◽

Hallmarks Of Cancer ◽

Aberrant Expression ◽

Cancer Diagnosis And Therapy

Polo-like kinases (Plks) are critical regulatory molecules during the cell cycle process. This family has five members: Plk1, 2, 3, 4, and 5. Plk4 has been identified as a master regulator of centriole replication, and its aberrant expression is closely associated with cancer development. In this review, we depict the DNA, mRNA, and protein structure of Plk4, and the regulation of Plk4 at a molecular level. Then we list the downstream targets of Plk4 and the hallmarks of cancer associated with these targets. The role of Plk4 in different cancers is also summarized. Finally, we review the inhibitors that target Plk4 in the hope of discovering effective anticancer drugs. From authors’ perspective, Plk4 might represent a valuable tumor biomarker and critical target for cancer diagnosis and therapy.

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PEAK1 promotes invasion and metastasis and confers drug resistance in breast cancer

10.21203/rs.3.rs-549884/v1 ◽

2021 ◽

Author(s):

xingang wang ◽

YAN ZHENG ◽

YU WANG

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Cell Growth ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Multi Drug Resistance ◽

Cancer Tissues

Abstract Background and AimsPseudopodium-enriched atypical kinase 1 (PEAK1) has reported to be upregulated in human malignancies and related with poor prognosis. Enhanced PEAK1 expression facilitates tumor cell survival, invasion, metastasis and chemoresistance. However, the role of PEAK1 in breast cancer is not clear. Here, we investigated the PEAK1 expression in breast cancer and analyzed its relation with clinicopathological status and chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated the role of PEAK1 on breast cancer cells in vitro and in vivo. MethodsImmunohistochemistry (IHC) was performed in 112 surgical resected breast cancer tissues. The associations between clinicopathological status, multi-drug resistance and PEAK1 expression were determined. Effect of PEAK1 overexpression or down-expression on proliferation, colony formation, invasion, migration, metastasis and Doxorubicin sensitivity in the MCF-7 cells in vitro and in vivo was detected. ResultsPEAK1 was overexpressed in breast cancer tissues and NAC -resistant breast cancer tissues. High PEAK1 expression was related with tumor size, high tumor grade, T stage, LN metastasis, recurrence, Ki-67 expression, Her-2 expression and multi-drug resistance. Targeting PEAK1 inhibited cell growth, invasion, metastasis and reversed chemoresistance to Doxorubicin in breast cancer cells in vitro and in vivo. ConclusionHigh PEAK1 expression was associated with invasion, metastasis and chemoresistance of breast cancers. Furthermore, targeting PEAK1 could inhibit cell growth and metastasis, and reverse chemoresistance in breast cancer cells, which provides an effective treatment strategies for breast cancer.

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Up-regulation of key glycolysis proteins in cancer development

Open Life Sciences ◽

10.1515/biol-2018-0068 ◽

2018 ◽

Vol 13 (1) ◽

pp. 569-581

Author(s):

Nicole Nowak ◽

Anna Kulma ◽

Jan Gutowicz

Keyword(s):

Cancer Cells ◽

Glucose Transporter ◽

Lactate Production ◽

Cancer Development ◽

Glucose Transporter 1 ◽

Expression Of Genes ◽

Glycolysis Pathway ◽

Cancer Cell Survival ◽

Glycolytic Rate

AbstractIn rapid proliferating cancer cells, there is a need for fast ATP and lactate production, therefore cancer cells turn off oxidative phosphorylation and turn on the so called "Warburg effect". This regulating the expression of genes involved in glycolysis. According to many studies, glucose transporter 1, which supplies glucose to the cell, is the most abundantly expressed transporter in cancer cells. Hexokinase 2, is one of four hexokinase isoenzymes, is also another highly expressed enzyme in cancer cells and it functions to enhance the glycolytic rate. The up-regulation of these two proteins has been established as an important factor in promoting development and metastasis in many types of cancer. Furthermore, other enzymes involved in glycolysis pathway such as phosphoglucose isomerase and glyceraldehyde 3-phosphate dehydrogenase, exhibit additional functions in promoting tumor growth in a non-glycolytic way. This review demonstrates the pivotal role of GLUT1, HK2, PGI and GAPDH in cancer development. In particular, we look at how the multifunctional proteins, PGI and GAPDH, affect cancer cell survival. We also present various clinical cancer cases in terms of the overexpression of selected proteins, which may be considered as a therapeutic target.

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The role of photodynamic therapy in overcoming cancer drug resistance

Photochemical & Photobiological Sciences ◽

10.1039/c4pp00495g ◽

2015 ◽

Vol 14 (8) ◽

pp. 1476-1491 ◽

Cited By ~ 122

Author(s):

Bryan Q. Spring ◽

Imran Rizvi ◽

Nan Xu ◽

Tayyaba Hasan

Keyword(s):

Drug Resistance ◽

Photodynamic Therapy ◽

Cancer Cells ◽

Cancer Drug ◽

Cancer Drug Resistance

This perspective highlights unique mechanisms of photodynamic therapy (PDT) that can be utilized to overcome classical drug resistance and re-sensitize resistant cancer cells for standard therapies.

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Role of AXL in invasion and drug resistance of breast and colon cancer cells

European Journal of Cancer ◽

10.1016/s0959-8049(16)61274-1 ◽

2016 ◽

Vol 61 ◽

pp. S79

Author(s):

W.M. Abdel-Rahman ◽

N.A. Al-khayyal ◽

V.A. Nair ◽

M.S. Ayad

Keyword(s):

Colon Cancer ◽

Drug Resistance ◽

Cancer Cells ◽

Colon Cancer Cells

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MP98-02 A POTENTIAL ROLE OF ABERRANT DNA METHYLATION IN THE CHEMORESISTANCE IN BLADDER CANCER CELLS. DNA METHYLATION INHIBITORS COULD RE-SENSITIZE DRUG-RESISTANCE BLADDER CANCER CELLS.

The Journal of Urology ◽

10.1016/j.juro.2017.02.3067 ◽

2017 ◽

Vol 197 (4S) ◽

Cited By ~ 1

Author(s):

Nobuo Shinkai ◽

Naotaka Nishiyama ◽

Stephanie Yi ◽

Christopher E. Duymich ◽

Tetsuya Shindo ◽

...

Keyword(s):

Dna Methylation ◽

Drug Resistance ◽

Bladder Cancer ◽

Cancer Cells ◽

Potential Role ◽

Bladder Cancer Cells ◽

Aberrant Dna Methylation ◽

Dna Methylation Inhibitors

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Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives

International Journal of Molecular Sciences ◽

10.3390/ijms21072286 ◽

2020 ◽

Vol 21 (7) ◽

pp. 2286 ◽

Cited By ~ 8

Author(s):

Stefania Raimondo ◽

Marzia Pucci ◽

Riccardo Alessandro ◽

Simona Fontana

Keyword(s):

Cancer Cells ◽

Extracellular Vesicles ◽

Immune Cell ◽

Immune Escape ◽

Immune Checkpoints ◽

Cancer Therapies ◽

Biological Functions ◽

Hallmarks Of Cancer ◽

Tumor Immune Escape

The modulation of the immune system is one of the hallmarks of cancer. It is now widely described that cancer cells are able to evade the immune response and thus establish immune tolerance. The exploration of the mechanisms underlying this ability of cancer cells has always attracted the scientific community and is the basis for the development of new promising cancer therapies. Recent evidence has highlighted how extracellular vesicles (EVs) represent a mechanism by which cancer cells promote immune escape by inducing phenotypic changes on different immune cell populations. In this review, we will discuss the recent findings on the role of tumor-derived extracellular vesicles (TEVs) in regulating immune checkpoints, focusing on the PD-L1/PD-1 axis.

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