A Cdh3-β-catenin-laminin signaling axis in a subset of breast tumor leader cells control leader cell polarization and directional collective migration

Hwang, Priscilla Y.; Mathur, Jairaj; Cao, Yanyang; Almeida, J. A. Afonso de; Ye, Jiayu; Morikis, Vasilios A.; Cornish, Daphne; Clarke, Maria; Stewart, Sheila A.; Pathak, Amit; Longmore, Gregory D.

doi:10.1016/j.devcel.2022.12.005

Cited by 15 publications

(18 citation statements)

References 71 publications

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“…Here we perform clustering on a dataset from Hwang et al, which studies collective cell migration of breast cancer [28]. During collective migration in vivo , breast cancer cells move as a cluster and prior work suggests that cells within the clusters can be heterogeneous [29].…”

Section: Resultsmentioning

confidence: 99%

“…Thus, Hwang et al used single cell sequencing to identify different cell populations within collectively migrating clusters, with the ultimate goal to understand how cells at the front, known as leader cells, may have unique gene signatures that allow them to lead migration. To induce migration, Hwang et al used biochemical and biomechanical gradients, and performed single cell sequencing analysis after migration had occured (GEO Accession number: GSE171203) [28]. After induction of biochemical gradient stromal-derived factor 1 (SDF1), single cell sequencing analysis of tumor clusters revealed 9 different cell population types and 1 primary cluster of leader cells with differential expression of Cadherin-3 (CDH3) [28].…”

Section: Resultsmentioning

confidence: 99%

“…To induce migration, Hwang et al used biochemical and biomechanical gradients, and performed single cell sequencing analysis after migration had occured (GEO Accession number: GSE171203) [28]. After induction of biochemical gradient stromal-derived factor 1 (SDF1), single cell sequencing analysis of tumor clusters revealed 9 different cell population types and 1 primary cluster of leader cells with differential expression of Cadherin-3 (CDH3) [28].…”

Section: Resultsmentioning

confidence: 99%

“…We calculated the differentially expressed genes by running the FindAllMarkers function in Seurat [4]. The primary goal behind this analysis was to determine whether CHAI cluster 5 cell population was enriched for CDH3, a demonstrated leader cell marker in the original study [28], as a way to validate cluster 5 is indeed the leader cell population. Our analysis demonstrates CDH3 is significantly upregulated in the CHAI-AvgSim leader cell cluster, when compared to other clusters.…”

Section: Chai Derives Validated Biological Insights In a Breast Cance...mentioning

confidence: 99%

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CHAI: Consensus Clustering Through Similarity Matrix Integration for Cell-Type Identification

Lodi,

Osei

et al. 2024

Preprint

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Several methods have been developed to computationally predict cell-types for single cell RNA sequencing (scRNAseq) data. As methods are developed, a common problem for investigators has been identifying the best method they should apply to their specific use-case. To address this challenge, we present CHAI (consensus Clustering tHrough similArIty matrix integratIon for single cell type identification), a wisdom of crowds approach for scRNAseq clustering. CHAI presents two competing methods which aggregate the clustering results from seven state of the art clustering methods: CHAI-AvgSim and CHAI-SNF. Both methods demonstrate improved performance on a diverse selection of benchmarking datasets, besides also outperforming a previous consensus clustering method. We demonstrate CHAI's practical use case by identifying a leader tumor cell cluster enriched with CDH3. CHAI provides a platform for multiomic integration, and we demonstrate CHAI-SNF to have improved performance when including spatial transcriptomics data. CHAI is intuitive and easily customizable; it provides a way for users to add their own clustering methods to the pipeline, or down-select just the ones they want to use for the clustering aggregation. CHAI is available as an open source R package on GitHub: https://github.com/lodimk2/chai

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Chai Derives Validated Biological Insights In a Breast Cance...mentioning

confidence: 99%

See 2 more Smart Citations

CHAI: Consensus Clustering Through Similarity Matrix Integration for Cell-Type Identification

Lodi,

Osei

et al. 2024

Preprint

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“…Leader cells also generate high protrusive forces and overcome extracellular matrix (ECM) resistance at the leading edge. Single-cell sequencing nd that CDH3 controls leader cell protrusion dynamics through local production of integrin/focal adhesion function [25] . Researchers also found that the remodeling and reorganization of cytoskeleton and cell matrix can change the traction force, thus regulating cell movement behavior in breast cancer [26] .…”

Section: Discussionmentioning

confidence: 99%

Traction force with extracellular matrix mediated by cytoskeleton had an effect on metastasis through SLC8A1 induced Wnt-β-catenin pathway in endometrial cancer

Zhou

et al. 2023

Preprint

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Endometrial cancer (EC) is a common malignant tumor of female reproductive system. It seriously affects women's health. The mechanical characteristics of EC have not been paid noticed. However, the mechanical characteristics of different types of EC are diverse. These characteristics will greatly influence the development and prognosis of cancer cells. In this study, we explored traction force in primary EC cells and EC cell lines for the first time. It was found that the traction force of primary EC cells or cell lines with metastatic capability was lower. Various clinicopathological features of EC patients are significantly associated with traction force. In addition, we also confirmed that SLC8A1 is the main molecule which had an effect on traction force. The stiffness of extracellular matrix (ECM) had an influence on its downstream cytoskeleton expression through SLC8A1, thus changing the traction force and metastatic capacity of EC cells. The mechanism behind the SLC8A1 may be related to Wnt-β- catenin pathway and ion-channel activity. SLC8A1 can significantly regulate the downstream cytoskeleton F-actin and promote EC cell metastasis. Therefore, in this study, we found that SLC8A1 is an important molecule that affects the mechanical characteristics of endometrial cancer. The molecular mechanism is through changing the cytoskeleton by regulating Wnt- β- catenin pathway.

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A systematic review on the culture methods and applications of 3D tumoroids for cancer research and personalized medicine

Kalla,

Pfneissl,

Mair

et al. 2024

Cell Oncol.

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Cancer is a highly heterogeneous disease, and thus treatment responses vary greatly between patients. To improve therapy efficacy and outcome for cancer patients, more representative and patient-specific preclinical models are needed. Organoids and tumoroids are 3D cell culture models that typically retain the genetic and epigenetic characteristics, as well as the morphology, of their tissue of origin. Thus, they can be used to understand the underlying mechanisms of cancer initiation, progression, and metastasis in a more physiological setting. Additionally, co-culture methods of tumoroids and cancer-associated cells can help to understand the interplay between a tumor and its tumor microenvironment. In recent years, tumoroids have already helped to refine treatments and to identify new targets for cancer therapy. Advanced culturing systems such as chip-based fluidic devices and bioprinting methods in combination with tumoroids have been used for high-throughput applications for personalized medicine. Even though organoid and tumoroid models are complex in vitro systems, validation of results in vivo is still the common practice. Here, we describe how both animal- and human-derived tumoroids have helped to identify novel vulnerabilities for cancer treatment in recent years, and how they are currently used for precision medicine.

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A Cdh3-β-catenin-laminin signaling axis in a subset of breast tumor leader cells control leader cell polarization and directional collective migration

Cited by 15 publications

References 71 publications

CHAI: Consensus Clustering Through Similarity Matrix Integration for Cell-Type Identification

CHAI: Consensus Clustering Through Similarity Matrix Integration for Cell-Type Identification

Traction force with extracellular matrix mediated by cytoskeleton had an effect on metastasis through SLC8A1 induced Wnt-β-catenin pathway in endometrial cancer

A systematic review on the culture methods and applications of 3D tumoroids for cancer research and personalized medicine

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