Emerging roles of ECM remodeling processes in cancer

Mohan, Vishnu; Das, Alakesh; Sagi, Irit

doi:10.1016/j.semcancer.2019.09.004

Cited by 243 publications

(181 citation statements)

References 157 publications

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“…In cancer, transformed cells are able to leave the tissue of origin, invade and home to metastatic niches-a process in which the ECM plays a fundamental role [35]. It is known that, in parallel to alterations in cancer cells, ECM remodeling enzymes (including MMPs) increase their levels; cancer-associated fibroblasts (CAFs), immune cells, and other stromal cells are recruited; various growth factors are secreted, and collagen deposition is induced, all contributing to ECM remodeling at the tumor site [36,37]. These series of events lead to increased ECM stiffness, abnormal cell-cell adhesion, up-regulation of integrin signaling and subsequent activation of downstream cascades, promoting tumor growth and progression [17,36,37].…”

Section: Ecm Deregulation In Pre-malignant Lesions and Gastric Cancermentioning

confidence: 99%

The Extracellular Matrix: An Accomplice in Gastric Cancer Development and Progression

Moreira

Pereira

Melo

et al. 2020

Cells

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The extracellular matrix (ECM) is a dynamic and highly organized tissue structure, providing support and maintaining normal epithelial architecture. In the last decade, increasing evidence has emerged demonstrating that alterations in ECM composition and assembly strongly affect cellular function and behavior. Even though the detailed mechanisms underlying cell-ECM crosstalk are yet to unravel, it is well established that ECM deregulation accompanies the development of many pathological conditions, such as gastric cancer. Notably, gastric cancer remains a worldwide concern, representing the third most frequent cause of cancer-associated deaths. Despite increased surveillance protocols, patients are usually diagnosed at advanced disease stages, urging the identification of novel diagnostic biomarkers and efficient therapeutic strategies. In this review, we provide a comprehensive overview regarding expression patterns of ECM components and cognate receptors described in normal gastric epithelium, pre-malignant lesions, and gastric carcinomas. Important insights are also discussed for the use of ECM-associated molecules as predictive biomarkers of the disease or as potential targets in gastric cancer.

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Section: Ecm Deregulation In Pre-malignant Lesions and Gastric Cancermentioning

confidence: 99%

The Extracellular Matrix: An Accomplice in Gastric Cancer Development and Progression

Moreira

Pereira

Melo

et al. 2020

Cells

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“…Furthermore, we consider important to highlight that tumor cells are able to modulate their extracellular microenvironment to avoid drug action [54]. According to the role of UGDH enzyme in HA expression, there are controversial data regarding the effect on the modulation of its expression.…”

Section: Discussionmentioning

confidence: 99%

Knockdown Of Udp-Glucose Dehydrogenase Facilitates Epirubicin-Resistance In MDA-MB-231 Breast Cancer Cells By Regulation Of Hyaluronan Synthesis.

Vitale

Caon

Parnigoni

et al. 2020

Preprint

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Background: The catalytic action of the UDP-glucose transferase dehydrogenase (UGDH) enzyme produces UDP-glucuronic acid (UDP-GlcUA). The main detoxifying pathway of Epirubicin (EPI) is via glucuronidation by the specific transferase UGT2B7 (UDP-Glucuronosyltransferase-2B7), adding UDP-GlcUA to generates 4´-O-b-D-glucuronyl-4´-epi-doxorubicin. UDP-GlcUA is also a precursor of several glycosaminoglycans (GAGs) like hyaluronan (HA). Therefore, the EPI detoxifying pathway might be associated with GAGs metabolism, related to drug deactivation and tumor resistance. This work aimed to evaluate the effect of knockdown on the UGDH gene on EPI response and HA metabolism in the aggressive breast cancer cells MDA-MB 231. Methods: MDA-MB-231 cells were transfected in vitro with UGDH-specific siRNA for UGDH knockdown and treated with EPI. Viability, apoptosis, and cytotoxicity effects were evaluated. EPI intracellular accumulation was analyzed by flow cytometry. Differences in extracellular matrix (ECM) were analyzed through a particle exclusion assay and the composition of HA using hyaluronidase. The soluble HA secreted was detected by an ELISA like assay. Besides, gene expression of HA synthase and hyaluronidase (HYAL) enzymes were analyzed by RT-qPCR. To analyze the effect of UGDH knockdown and EPI treatment on autophagy, we evaluated the expression of the autophagosome marker, LC3-II by RT-qPCR and western blot, and its subcellular localization by confocal microscopy. Results: EPI accumulation increased during UGDH knockdown, but it was observed a decrease in cell death. HA synthesis and HA coated around the cells increased. In turn, it was found up-regulation of the expression of HYALs. Within the mechanisms activated by tumor cells to avoid EPI activity, an increase in autophagy was detected. Conclusions: for the first time we show that an increase in the expression, deposition and catabolism of HA positively contributed to the development of a resistant phenotype in breast cancer cells by a mechanism associated to sugar metabolism, specifically of UDP-GlcUA .

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“…A decrease in the concentration of this protein leads to an increase in metalloproteinase concentration, thereby increasing their activity. Metalloproteinase activity also increases via the Fas/Fas2 signaling pathway [167][168][169]. When transporting the Fas ligand to the target cell, exosomes contribute to the activation of the Fas/Fas2 pathway, and thus increase the activity of the proteins responsible for the reorganization of the extracellular matrix [170,171].…”

Section: Exosomesmentioning

confidence: 99%

Important players in carcinogenesis as potential targets in cancer therapy: an update

2020

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The development of cancer is a problem that has accompanied mankind for years. The growing number of cases, emerging drug resistance, and the need to reduce the serious side effects of pharmacotherapy are forcing scientists to better understand the complex mechanisms responsible for the initiation, promotion, and progression of the disease. This paper discusses the modulation of the particular stages of carcinogenesis by selected physiological factors, including: acetylcholine (ACh), peroxisome proliferator-activated receptors (PPAR), fatty acid-binding proteins (FABPs), Bruton's tyrosine kinase (Btk), aquaporins (AQPs), insulin-like growth factor-2 (IGF-2), and exosomes. Understanding their role may contribute to the development of more effective and safer therapies based on new binding sites.

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Emerging roles of ECM remodeling processes in cancer

Cited by 243 publications

References 157 publications

The Extracellular Matrix: An Accomplice in Gastric Cancer Development and Progression

The Extracellular Matrix: An Accomplice in Gastric Cancer Development and Progression

Knockdown Of Udp-Glucose Dehydrogenase Facilitates Epirubicin-Resistance In MDA-MB-231 Breast Cancer Cells By Regulation Of Hyaluronan Synthesis.

Important players in carcinogenesis as potential targets in cancer therapy: an update

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