Activation of Epithelial-Mesenchymal Transition and Altered β-Catenin Signaling in a Novel Indian Colorectal Carcinoma Cell Line

Mylavarapu, Sanghamitra; Kumar, Harsh; Kumari, Smita; Sravanthi, L. S.; Jain, Mayank; Basu, Aninda; Biswas, Manjusha; Mylavarapu, Sivaram V. S.; Das, Asmita; Roy, Moni

doi:10.3389/fonc.2019.00054

Cited by 15 publications

(14 citation statements)

References 64 publications

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“…Higher expression level of β-catenin was also achieved over time when HCEC-1CT were exposed to exosomes derived from metastatic SW620, and its localization into the cell nuclei was observed after three-day incubation. Aberrant Wnt signaling is a prominent feature of several cancers, especially CRCs, which was found in 90% of cases to exhibit overexpression of β-catenin [ 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

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A Possible Role of FZD10 Delivering Exosomes Derived from Colon Cancers Cell Lines in Inducing Activation of Epithelial–Mesenchymal Transition in Normal Colon Epithelial Cell Line

Scavo

Rizzi

Depalo

et al. 2020

IJMS

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Exosomes belong to the family of extracellular vesicles released by every type of cell both in normal and pathological conditions. Growing interest in studies indicates that extracellular vesicles, in particular, the fraction named exosomes containing lipids, proteins and nucleic acid, represent an efficient way to transfer functional cargoes between cells, thus combining all the other cell–cell interaction mechanisms known so far. Only a few decades ago, the involvement of exosomes in the carcinogenesis in different tissues was discovered, and very recently it was also observed how they carry and modulate the presence of Wnt pathway proteins, involved in the carcinogenesis of gastrointestinal tissues, such as Frizzled 10 protein (FZD10), a membrane receptor for Wnt. Here, we report the in vitro study on the capability of tumor-derived exosomes to induce neoplastic features in normal cells. Exosomes derived from two different colon cancer cell lines, namely the non-metastatic CaCo-2 and the metastatic SW620, were found to deliver, in both cases, FZD10, thus demonstrating the ability to reprogram normal colonic epithelial cell line (HCEC-1CT). Indeed, the acquisition of specific mesenchymal characteristics, such as migration capability and expression of FZD10 and markers of mesenchymal cells, was observed. The exosomes derived from the metastatic cell line, characterized by a level of FZD10 higher than the exosomes extracted from the non-metastatic cells, were also more efficient in stimulating EMT activation. The overall results suggest that FZD10, delivered by circulating tumor-derived exosomes, can play a relevant role in promoting the CRC carcinogenesis and propagation.

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Section: Discussionmentioning

confidence: 99%

“…Western blotting analysis was performed for total proteins extracted from exosomes derived from CaCo-2 and SW620 and for HCEC-1CT cells, untreated or treated with exosomes derived from both cancer cell lines, as previously described [ 39 ]. Untreated cells maintained in culture medium for 24 h were used as control.…”

Section: Methodsmentioning

confidence: 99%

A Possible Role of FZD10 Delivering Exosomes Derived from Colon Cancers Cell Lines in Inducing Activation of Epithelial–Mesenchymal Transition in Normal Colon Epithelial Cell Line

Scavo

Rizzi

Depalo

et al. 2020

IJMS

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“…β-catenin is sequestered and maintained by cadherins at adherens junctional complexes [56]. However, once EMT or EndMT is activated, β-catenin takes on a new role as a signaling molecule for the Wnt pathway as it disassociates from the cadherins at the membrane, translocates to the nucleus and binds to the TCF/LEF family of transcription factors to activate EMT and EndMT transcription factors including Snai1 [57,58]. Computational modeling of transcription factors regulating EMT in RPE identified lymphoid enhancer-binding factor 1 (LEF-1) as one of the candidate nodes in the EMT transcriptional regulatory network of RPE [59].…”

Section: Role Of Cytokine-mediated Signaling Pathwaysmentioning

confidence: 99%

EMT and EndMT: Emerging Roles in Age-Related Macular Degeneration

Shu

Butcher

Saint‐Geniez

2020

IJMS

175

138

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Epithelial–mesenchymal transition (EMT) and endothelial–mesenchymal transition (EndMT) are physiological processes required for normal embryogenesis. However, these processes can be hijacked in pathological conditions to facilitate tissue fibrosis and cancer metastasis. In the eye, EMT and EndMT play key roles in the pathogenesis of subretinal fibrosis, the end-stage of age-related macular degeneration (AMD) that leads to profound and permanent vision loss. Predominant in subretinal fibrotic lesions are matrix-producing mesenchymal cells believed to originate from the retinal pigment epithelium (RPE) and/or choroidal endothelial cells (CECs) through EMT and EndMT, respectively. Recent evidence suggests that EMT of RPE may also be implicated during the early stages of AMD. Transforming growth factor-beta (TGFβ) is a key cytokine orchestrating both EMT and EndMT. Investigations in the molecular mechanisms underpinning EMT and EndMT in AMD have implicated a myriad of contributing factors including signaling pathways, extracellular matrix remodelling, oxidative stress, inflammation, autophagy, metabolism and mitochondrial dysfunction. Questions arise as to differences in the mesenchymal cells derived from these two processes and their distinct mechanistic contributions to the pathogenesis of AMD. Detailed discussion on the AMD microenvironment highlights the synergistic interactions between RPE and CECs that may augment the EMT and EndMT processes in vivo. Understanding the differential regulatory networks of EMT and EndMT and their contributions to both the dry and wet forms of AMD can aid the development of therapeutic strategies targeting both RPE and CECs to potentially reverse the aberrant cellular transdifferentiation processes, regenerate the retina and thus restore vision.

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“…EMT is an important mechanism that affects the invasion and metastasis of CRC ( 21 ). Several growth factors, such as TGF-β and epidermal growth factor, mediate EMT ( 22 , 23 ). Notably, the results of the present study demonstrated that TGF-β induced miR-325-3p expression.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑325‑3p contributes to colorectal carcinoma by targeting cytokeratin 18

et al. 2021

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Colorectal carcinoma (CRC) is one of the most common malignant tumors. The present study aimed to investigate a non-invasive molecular marker that can evaluate the diagnosis and potential molecular mechanism of CRC. Microarray assays and reverse transcription-quantitative PCR analysis demonstrated that microRNA (miR)-325-3p expression was significantly increased in both tissues and serum samples of patients with CRC. In addition, miR-325-3p expression in the tissues and serum was significantly associated with differentiation, TNM stage and lymph node metastasis. The results of the dual-luciferase reporter assay and western blot analysis revealed that cytokeratin 18 (CK18) is a target gene of miR-325-3p. Furthermore, treatment with transforming growth factor (TGF)-β increased miR-325-3p expression in a time-dependent manner. Conversely, TGF-β decreased CK18 expression at 48 and 72 h. Western blot analysis demonstrated that TGF-β1 significantly decreased the expression of the epithelial marker, CK18, and increased the expression of the mesenchymal markers, α-SMA and vimentin. Notably, these effects were reversed following inhibition of miR-325-3p expression. Taken together, the results of the present study suggest that miR-325-3p is a key regulator of TGF-β-induced CK18 downregulation. Thus, elevated levels of miR-325-3p is an important factor affecting epithelial-to-mesenchymal transition, and is likely to be a molecular marker in the progression of CRC and act as a potential therapeutic target.

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Activation of Epithelial-Mesenchymal Transition and Altered β-Catenin Signaling in a Novel Indian Colorectal Carcinoma Cell Line

Cited by 15 publications

References 64 publications

A Possible Role of FZD10 Delivering Exosomes Derived from Colon Cancers Cell Lines in Inducing Activation of Epithelial–Mesenchymal Transition in Normal Colon Epithelial Cell Line

A Possible Role of FZD10 Delivering Exosomes Derived from Colon Cancers Cell Lines in Inducing Activation of Epithelial–Mesenchymal Transition in Normal Colon Epithelial Cell Line

EMT and EndMT: Emerging Roles in Age-Related Macular Degeneration

MicroRNA‑325‑3p contributes to colorectal carcinoma by targeting cytokeratin 18

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