Metadherin-mediated mechanisms in human malignancies

2021 ◽  
Author(s):  
Yuyuan Chen ◽  
Sheng Huang ◽  
Rong Guo ◽  
Dedian Chen
Keyword(s):  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Metastatic Potential ◽  
Potential Therapeutic Target ◽  
Mesenchymal Transition ◽  
Cancer Initiation ◽  
Related Proteins ◽  
Multiple Signaling ◽  
Novel Protein

Metadherin (MTDH) has been recognized as a novel protein that is critical for the progression of multiple types of human malignancies. Studies have reported that MTDH enhances the metastatic potential of cancer cells by regulating multiple signaling pathways. miRNAs and various tumor-related proteins have been shown to interact with MTDH, making it a potential therapeutic target as well as a biomarker in human malignancies. MTDH plays a critical role in inflammation, angiogenesis, hypoxia, epithelial–mesenchymal transition and autophagy. In this review, we present the function and mechanisms of MTDH for cancer initiation and progression.

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 Knockdown of 14-3-3γ Suppresses Epithelial–Mesenchymal Transition and Reduces Metastatic Potential of Human Non-small Cell Lung Cancer Cells

2018 ◽  
Vol 38 (6) ◽  
pp. 3507-3514 ◽  
Author(s):  
PRITSANA RAUNGRUT ◽  
ANUSARA WONGKOTSILA ◽  
NIDANUT CHAMPOOCHANA ◽  
KRIENGSAK LIRDPRAPAMONGKOL ◽  
JISNUSON SVASTI ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Potential ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung ◽  
Mesenchymal Transition

scholarly journals Emerging Autophagy Functions Shape the Tumor Microenvironment and Play a Role in Cancer Progression - Implications for Cancer Therapy

2020 ◽  
Vol 10 ◽  
Author(s):  
Silvina Odete Bustos ◽  
Fernanda Antunes ◽  
Maria Cristina Rangel ◽  
Roger Chammas
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Stress Responses ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Potential ◽  
Secretory Proteins ◽  
Mesenchymal Transition ◽  
Independent Functions

The tumor microenvironment (TME) is a complex environment where cancer cells reside and interact with different types of cells, secreted factors, and the extracellular matrix. Additionally, TME is shaped by several processes, such as autophagy. Autophagy has emerged as a conserved intracellular degradation pathway for clearance of damaged organelles or aberrant proteins. With its central role, autophagy maintains the cellular homeostasis and orchestrates stress responses, playing opposite roles in tumorigenesis. During tumor development, autophagy also mediates autophagy-independent functions associated with several hallmarks of cancer, and therefore exerting several effects on tumor suppression and/or tumor promotion mechanisms. Beyond the concept of degradation, new different forms of autophagy have been described as modulators of cancer progression, such as secretory autophagy enabling intercellular communication in the TME by cargo release. In this context, the synthesis of senescence-associated secretory proteins by autophagy lead to a senescent phenotype. Besides disturbing tumor treatment responses, autophagy also participates in innate and adaptive immune signaling. Furthermore, recent studies have indicated intricate crosstalk between autophagy and the epithelial-mesenchymal transition (EMT), by which cancer cells obtain an invasive phenotype and metastatic potential. Thus, autophagy in the cancer context is far broader and complex than just a cell energy sensing mechanism. In this scenario, we will discuss the key roles of autophagy in the TME and surrounding cells, contributing to cancer development and progression/EMT. Finally, the potential intervention in autophagy processes as a strategy for cancer therapy will be addressed.

scholarly journals Does Direct and Indirect Exposure to Ionising Radiation Influence the Metastatic Potential of Breast Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 236 ◽  
Author(s):  
Munira A. Kadhim ◽  
Ammar Mayah ◽  
Susan A. Brooks
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Indirect Effects ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Potential ◽  
Ionising Radiation ◽  
Surface Proteins ◽  
In Vivo Models ◽  
Mesenchymal Transition

Ionising radiation (IR) is commonly used for cancer therapy; however, its potential influence on the metastatic ability of surviving cancer cells exposed directly or indirectly to IR remains controversial. Metastasis is a multistep process by which the cancer cells dissociate from the initial site, invade, travel through the blood stream or lymphatic system, and colonise distant sites. This complex process has been reported to require cancer cells to undergo epithelial-mesenchymal transition (EMT) by which the cancer cells convert from an adhesive, epithelial to motile, mesenchymal form and is also associated with changes in glycosylation of cell surface proteins, which may be functionally involved in metastasis. In this paper, we give an overview of metastatic mechanisms and of the fundamentals of cancer-associated glycosylation changes. While not attempting a comprehensive review of this wide and fast moving field, we highlight some of the accumulating evidence from in vitro and in vivo models for increased metastatic potential in cancer cells that survive IR, focusing on angiogenesis, cancer cell motility, invasion, and EMT and glycosylation. We also explore the indirect effects in cells exposed to exosomes released from irradiated cells. The results of such studies need to be interpreted with caution and there remains limited evidence that radiotherapy enhances the metastatic capacity of cancers in a clinical setting and undoubtedly has a very positive clinical benefit. However, there is potential that this therapeutic benefit may ultimately be enhanced through a better understanding of the direct and indirect effects of IR on cancer cell behaviour.

scholarly journals OCT4 Potentiates Radio-Resistance and Migration Activity of Rectal Cancer Cells by Improving Epithelial-Mesenchymal Transition in a ZEB1 Dependent Manner

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Minghai Shao ◽  
Tienan Bi ◽  
Wenxiu Ding ◽  
Changhui Yu ◽  
Caiping Jiang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Rectal Cancer Patient ◽  
Critical Role ◽  
Patient Treatment ◽  
Dependent Manner ◽  
Migration Activity ◽  
Resistance Development ◽  
Mesenchymal Transition

Radiotherapy is an important strategy for rectal cancer patient treatment. However, the efficiency of radiation is usually poor, especially in patients with advanced stage rectal cancer due to the radio-resistance developed. At the present study, OCT4 was found to play a critical role in radio-resistance development in human rectal cancer cells by improving the epithelial-mesenchymal transition process (EMT). Endogenous OCT4 expression could confer resistant phonotype on human rectal cancer cells, which was supported by the data from clonogenic forming assay and cell cycle arrest recovering experiment. EMT related transcription factor ZEB1 might take part in the radio-resistance induced by OCT4, as its expression could be upregulated by OCT4 and its silence could reverse the OCT4 induced resistance to radiation in SW480 cells. More interestingly, CHK1 was also upregulated in OCT4/ZEB1 dependent manner conferring stronger DNA damage repair activity on cancer cells, which might explain the underlying mechanisms why OCT4/ZEB1 axis could promote the resistance of human rectal cancer cell to radiation. Taken together, our results provided a novel mechanism for radio-resistance development in human rectal cancer cells and a new target to overcome this resistance.

scholarly journals Unraveling the Molecular Nexus between GPCRs, ERS, and EMT

2021 ◽  
Vol 2021 ◽  
pp. 1-23
Author(s):  
Niti Kumari ◽  
Somrudee Reabroi ◽  
Brian J. North
Keyword(s):  
Cancer Cells ◽  
Signaling Pathways ◽  
Cancer Cell ◽  
Cancer Biology ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Tumor Formation ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Tumor Dissemination

G protein-coupled receptors (GPCRs) represent a large family of transmembrane proteins that transduce an external stimulus into a variety of cellular responses. They play a critical role in various pathological conditions in humans, including cancer, by regulating a number of key processes involved in tumor formation and progression. The epithelial-mesenchymal transition (EMT) is a fundamental process in promoting cancer cell invasion and tumor dissemination leading to metastasis, an often intractable state of the disease. Uncontrolled proliferation and persistent metabolism of cancer cells also induce oxidative stress, hypoxia, and depletion of growth factors and nutrients. These disturbances lead to the accumulation of misfolded proteins in the endoplasmic reticulum (ER) and induce a cellular condition called ER stress (ERS) which is counteracted by activation of the unfolded protein response (UPR). Many GPCRs modulate ERS and UPR signaling via ERS sensors, IRE1α, PERK, and ATF6, to support cancer cell survival and inhibit cell death. By regulating downstream signaling pathways such as NF-κB, MAPK/ERK, PI3K/AKT, TGF-β, and Wnt/β-catenin, GPCRs also upregulate mesenchymal transcription factors including Snail, ZEB, and Twist superfamilies which regulate cell polarity, cytoskeleton remodeling, migration, and invasion. Likewise, ERS-induced UPR upregulates gene transcription and expression of proteins related to EMT enhancing tumor aggressiveness. Though GPCRs are attractive therapeutic targets in cancer biology, much less is known about their roles in regulating ERS and EMT. Here, we will discuss the interplay in GPCR-ERS linked to the EMT process of cancer cells, with a particular focus on oncogenes and molecular signaling pathways.

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