Cell–cell adhesion: linking Wnt/β-catenin signaling with partial EMT and stemness traits in tumorigenesis

Basu, Sayon; Cheriyamundath, Sanith; Ben-Ze’ev, Avri

doi:10.12688/f1000research.15782.1

Cited by 147 publications

(118 citation statements)

References 92 publications

(106 reference statements)

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“…Antibodies purchased were mouse anti‐FLAG M2 (Sigma), anti‐β‐catenin (Santa Cruz), anti‐SCRIB (Santa Cruz for immunoprecipitation or Cell signaling for Western Blot detection), and anti‐LRR (in‐house generated, see ref. []). The following sequences of siRNA were used to target SCRIB: SCRIB (#01) GACCGCGUCCUCUCUAUUA, SCRIB (#02) GGACGACGAGGGCGAUAUUC.…”

Section: Methodsmentioning

confidence: 99%

“…In the absence of Wnts, β‐catenin is constitutively targeted for proteolysis impairing transcriptional events . In organized epithelial sheets, Wnt signaling is low but the contribution of scaffold proteins to the inhibition of the Wnt/β‐catenin remains unclear and might be due to the inhibitory role of adherens junctions and apical‐basal polarity complexes …”

Section: Introductionmentioning

confidence: 99%

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The Tumor Suppressor SCRIB is a Negative Modulator of the Wnt/β‐Catenin Signaling Pathway

et al. 2019

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SCRIB is a scaffold protein containing leucine‐rich repeats (LRR) and PSD‐95/Dlg‐A/ZO‐1 domains (PDZ) that localizes at the basolateral membranes of polarized epithelial cells. Deregulation of its expression or localization leads to epithelial defects and tumorigenesis in part as a consequence of its repressive role on several signaling pathways including AKT, ERK, and HIPPO. In the present work, a proteomic approach is used to characterize the protein complexes associated to SCRIB and its paralogue LANO. Common and specific sets of proteins associated to SCRIB and LANO by MS are identified and an extensive landscape of their associated networks and the first comparative analysis of their respective interactomes are provided. Under proteasome inhibition, it is further found that SCRIB is associated to the β‐catenin destruction complex that is central in Wnt/β‐catenin signaling, a conserved pathway regulating embryonic development and cancer progression. It is shown that the SCRIB/β‐catenin interaction is potentiated upon Wnt3a stimulation and that SCRIB plays a repressing role on Wnt signaling. The data thus provide evidence for the importance of SCRIB in the regulation of the Wnt/β‐catenin pathway.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Tumor Suppressor SCRIB is a Negative Modulator of the Wnt/β‐Catenin Signaling Pathway

et al. 2019

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“…[ 57,134b,143b ] In 3D TMEs in vivo, where malignant cells reach protective niches in the body, cell motility and adhesion are apparently critical steps in invasive metastatic processes. [ 173 ] Each cell objectively requires optimal chemical, biological, and mechanical growth conditions to modulate cell behaviors in 3D context. A series of microfluidic 3D models or 3D perfusion systems are developed to accurately recapitulate the cell microenvironments and transcoelomic routes and control the effects of soluble cues and different cell types on cell adhesion, migration, and invasiveness.…”

Section: Instructive Cell Constructs In Tissue Engineering and Precismentioning

confidence: 99%

Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

Yang

Zhao

2020

Advanced Science

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mouse intestinal stem cells and primary colorectal cancer cells can be propagated in vitro long term, [1] there is an urgent need to develop more physiologically relevant, efficient, and robust precise oncology models that closely recapitulate the genetic and morphological heterogeneous composition and mimic the arrangement pattern of cancer cells in the original tumor. [2] To our knowledge in biomedical research, hydrogel is the best tool to reconstruct precise oncology models in vitro, especially tumor organoid, which not only recapitulates in vivo biology and microenvironmental factors, but also at large extent allows side-by-side comparison to evaluate the translational potential of 3D model systems to the patients. [2a,3] Generally, hydrogels are mainly composed of hydrophilic polymeric scaffolds that absorb large amounts of water, so the hydrogel matrix better mimics elastic and viscoelastic properties in ECM and microscale topographies of cell matrices, which controls proper cell morphology, directs viable cell behaviors, and drives in vivo fundamental cell-cell or cell-ECM interactions. [4] To recapitulate pathophysiological features of human tumors and imitate various aspects of human tumorigenesis in vivo, hydrogels can provide a realistic platform to establish a useful bridge between in vitro assays and in vivo cell microenvironments. In current biomedical applications, there are many kinds of hydrogels to be developed to mimic the biological properties of ECM, such Designer self-assembling peptides form the entangled nanofiber networks in hydrogels by ionic-complementary self-assembly. This type of hydrogel has realistic biological and physiochemical properties to serve as biomimetic extracellular matrix (ECM) for biomedical applications. The advantages and benefits are distinct from natural hydrogels and other synthetic or semisynthetic hydrogels. Designer peptides provide diverse alternatives of main building blocks to form various functional nanostructures. The entangled nanofiber networks permit essential compositional complexity and heterogeneity of engineering cell microenvironments in comparison with other hydrogels, which may reconstruct the tumor microenvironments (TMEs) in 3D cell cultures and tissue-specific modeling in vitro. Either ovarian cancer progression or recurrence and relapse are involved in the multifaceted TMEs in addition to mesothelial cells, fibroblasts, endothelial cells, pericytes, immune cells, adipocytes, and the ECM. Based on the progress in common hydrogel products, this work focuses on the diverse designer self-assembling peptide hydrogels for instructive cell constructs in tissue-specific modeling and the precise oncology remodeling for ovarian cancer, which are issued by several research aspects in a 3D context. The advantages and significance of designer peptide hydrogels are discussed, and some common approaches and coming challenges are also addressed in current complex tumor diseases.

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“…The signaling conveyed by cell adhesion and with the underlying ECM is closely coordinated with gene regulation during normal tissue homeostasis [16]. Disruption of cell adhesion, the subsequent changes in adhesion-mediated signal transduction, and the increase in cell motility are characteristics in the development of invasive metastatic cancer [17]. It has been reported that alterations in cell-cell and cell-ECM adhesion promote cancer cell invasion, intravasation and extravasation [18].…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarkers associated with ovarian cancer based on transcriptome sequencing

chen

Peng

2019

Preprint

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Objective: This study aimed to explore more biomarkers associated with ovarian cancer.Methods: Cell lines SKOV-3 (ovarian serous carcinoma cells) and MCV152 (benign ovarian epithelial tumor cell) were used in this study and performed transcriptome sequencing. The differentially expressed genes (DEGs) between ovarian cancer cells (SKOV-3) and controls (MCV152) were identified, followed by function enrichment analysis. The expression levels of genes involved in the key pathway were validated through PCR and western blot analyses.Results: Total 2,020 upregulated and 1,673 downregulated DEGs were obtained between SKOV3 and MCV152 cells. The upregulated and downregulated DEGs were significantly associated with cell adhesion. In addition, the upregulated DEGs were significantly involved in pathways of ECM-receptor interaction, and the downregulated DEGs were involved in PI3K-Akt signaling pathway. PCR and western blot analyses showed that genes (proteins) expression related to PI3K-Akt signaling pathway were in consistent with bioinformatics analysis. Conclusion:Cell adhesion and extracellular matrix (ECM)-receptor interaction may play an important role in the invasion of ovarian cancer. PI3K-Akt signaling pathway may be involved in the progression of ovarian cancer by up-regulating ANGPT2, FGF18, ITGB4 and ITGB8, and downregulating AKT3 and PIK3AP1.

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Cell–cell adhesion: linking Wnt/β-catenin signaling with partial EMT and stemness traits in tumorigenesis

Cited by 147 publications

References 92 publications

The Tumor Suppressor SCRIB is a Negative Modulator of the Wnt/β‐Catenin Signaling Pathway

The Tumor Suppressor SCRIB is a Negative Modulator of the Wnt/β‐Catenin Signaling Pathway

Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

Identification of biomarkers associated with ovarian cancer based on transcriptome sequencing

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