Compression-induced expression of glycolysis genes in CAFs correlates with EMT and angiogenesis gene expression in breast cancer

Kim, Baek Gil; Sung, Jin Sol; Jang, Yeonsue; Jin, Yoon; Kang, Suki; Han, Hyunho; Lee, Juhyun; Cho, Nam Hoon

doi:10.1038/s42003-019-0553-9

Cited by 54 publications

(59 citation statements)

References 52 publications

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“…Compression may contribute to tumor cell survival in the hypoxic conditions by activating glycolysis genes and adapting cell metabolism and microRNA (miRNA). It was observed that metabolic, EMT-related, and angiogenesis genes were all upregulated in compressed patientderived cancer-associated fibroblasts compared to the static control (Kim et al, 2019). In vitro compression models also found upregulated glycolysis genes in MDA-MB-231 and migration-related genes in SK-BR-3 cells.…”

Section: Compressionmentioning

confidence: 95%

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The Role of Microenvironmental Cues and Mechanical Loading Milieus in Breast Cancer Cell Progression and Metastasis

Riehl

Kim

Bouzid

et al. 2021

Front. Bioeng. Biotechnol.

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Cancer can disrupt the microenvironments and mechanical homeostatic actions in multiple scales from large tissue modification to altered cellular signaling pathway in mechanotransduction. In this review, we highlight recent progresses in breast cancer cell mechanobiology focusing on cell-microenvironment interaction and mechanical loading regulation of cells. First, the effects of microenvironmental cues on breast cancer cell progression and metastasis will be reviewed with respect to substrate stiffness, chemical/topographic substrate patterning, and 2D vs. 3D cultures. Then, the role of mechanical loading situations such as tensile stretch, compression, and flow-induced shear will be discussed in relation to breast cancer cell mechanobiology and metastasis prevention. Ultimately, the substrate microenvironment and mechanical signal will work together to control cancer cell progression and metastasis. The discussions on breast cancer cell responsiveness to mechanical signals, from static substrate and dynamic loading, and the mechanotransduction pathways involved will facilitate interdisciplinary knowledge transfer, enabling further insights into prognostic markers, mechanically mediated metastasis pathways for therapeutic targets, and model systems required to advance cancer mechanobiology.

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Section: Compressionmentioning

confidence: 95%

“…Compression Kim et al, 2019 Compression may contribute to tumor cell survival in hypoxic conditions by activating glycolysis genes and adapting cell metabolism and miRNA. Metabolic, EMT-related, and angiogenesis genes are upregulated in compressed cancer-associated fibroblasts compared to static control.…”

Section: Stretchmentioning

confidence: 99%

The Role of Microenvironmental Cues and Mechanical Loading Milieus in Breast Cancer Cell Progression and Metastasis

Riehl

Kim

Bouzid

et al. 2021

Front. Bioeng. Biotechnol.

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“…As a result, the application of mechanical compression on living cells, such as cancerous [5,[9][10][11][12][13][14][15][16][17][18][19], non-cancerous and stromal cells [20][21][22], neurons [23] and chondrocytes [24], has gained importance in recent years. Compression applied on cancer types, such as breast [5,16,18,19], brain [13], pancreatic [9] and ovarian [17,25] cancer cells, resulted in more invasive and metastatic forms. While indicative, previous studies all point out the need for further investigations to understand the e↵ect of compressive mechanical stimuli in metastasis of di↵erent cancer types, for example ovarian cancer [17,25,26].…”

Section: Introductionmentioning

confidence: 99%

“…Tse et al developed a transmembrane pressure device applying compression on cancer cells; however, this is a bulk system that can apply constant force, lacking automation of modulation of the applied pressure [5]. Similar static setups in bulk systems were used more recently by Kim et al [18] and Li et al [19] on cancer associated stromal cells. Although compression e↵ects on other cell types, such as fibroblasts, neurons, chondrocytes, have been shown using microfluidic devices, compression e↵ects in cancer on-chip need more investigation.…”

Section: Introductionmentioning

confidence: 99%

A flexible micro-piston device for mechanical cell stimulation and compression in microfluidic settings

Önal

Alkaisi

Nock

2021

Preprint

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Evidence continues to emerge that cancer is not only a disease of genetic mutations, but also of altered mechanobiological profiles of the cells and microenvironment. This mutation-independent element might be a key factor in promoting development and spread of cancer. Biomechanical forces regulate tumor microenvironment by solid stress, matrix mechanics, interstitial pressure and flow. Compressive stress by tumor growth and stromal tissue alters the cell deformation, and recapitulates the biophysical properties of cells to grow, differentiate, spread or invade. Such a solid stress can be introduced externally to change the cell response and to mechanically induce cell lysis by dynamic compression. In this work we report a microfluidic cell-culture platform with an integrated, actively-modulated actuator for the application of compressive forces on cancer cells. Our platform is composed of a control microchannel in a top layer for introducing external force and a polydimethylsiloxane (PDMS) membrane with monolithically integrated actuators. The integrated actuator, herein called micro-piston, was used to apply compression on SKOV-3 ovarian cancer cells in a dynamic and controlled manner by modulating applied gas pressure, localization, shape and size of the micro-piston. We report fabrication of the platform, characterization of the mechanical actuator experimentally and computationally, as well as cell loading and culture in the device. We further show use of the actuator to perform both, repeated dynamic cell compression at physiological pressure levels, and end-point mechanical cell lysis, demonstrating suitability for mechanical stimulation to study the role of compressive forces in cancer microenvironments.

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“…The EMT participates in tumor invasion and metastasis through multiple pathways. Many studies have indicated the EMT is strongly linked to breast cancer development [11][12][13].…”

mentioning

confidence: 99%

Downregulation of GLYAT facilities tumor growth and metastasis and poor clinical outcomes through the PI3K/AKT/Snail pathway in human breast cancer

Tian

Jiang

et al. 2020

Preprint

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Background The Glycine N-acyltransferase (GLYAT) gene encodes a protein that catalyzes the transfer of acyl groups from acyl CoA to glycine, resulting in acyl glycine and coenzyme A. Aberrant GLYAT expression is associated with several malignant tumors, but its clinical importance in malignant tumors, especially human breast cancer (BC), has yet to be fully addressed. This study aims to evaluate the clinical function of GLYAT in BC patients. Methods GLYAT expression was determined by immune blot and immunohistochemistry in three BC cell lines and primary cancer tissues. The MDA-MB 231 cell line was used for GLYAT gene knockdown experiments while the MCF7 cell line for overexpression experiments. Colony formation experiments, soft agar experiments, and transwell assays were utilized for further inspection of cell migration and proliferation capabilities. Immunofluorescence and western blot were used to detect markers of the epithelial-mesenchymal transition (EMT) and changes in the PI3K/AKT/Snail pathway. The role of GLYAT in tumor growth and metastasis was also assessed in nude mice in vivo. Also, a correlation analysis was performed between clinicopathological features and GLYAT expression in BC patients. Results GLYAT was decreased in human BC tissues and cell lines. Functional analysis showed that knockdown of GLYAT augmented BC cell proliferation in vitro and in vivo. However, this phenomenon was reversed when GLYAT was overexpressed in the transfected cells. Moreover, GLYAT inhibited the migratory properties of BC cells, likely through the activation of PI3K/ATK/Snail signaling, which subsequently induced the EMT. IHC analysis indicated that GLYAT was decreased in human BC tissues and lower GLYAT expression was correlated with histological grade, tumor TNM stage, Ki-67 status, and poorer survival in BC patients. Furthermore, lower GLYAT expression seemed as an independent risk factor related to poor prognosis in BC patients based on Cox regression analyses. Conclusions Our findings demonstrate that downregulation of GLYAT expression in human breast cancer is correlated with EMT via the PI3K/ATK/Snail pathway and is also associated with histological grade, tumor TNM stage, Ki-67 status, and poor survival in breast cancer patients.

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Compression-induced expression of glycolysis genes in CAFs correlates with EMT and angiogenesis gene expression in breast cancer

Cited by 54 publications

References 52 publications

The Role of Microenvironmental Cues and Mechanical Loading Milieus in Breast Cancer Cell Progression and Metastasis

The Role of Microenvironmental Cues and Mechanical Loading Milieus in Breast Cancer Cell Progression and Metastasis

A flexible micro-piston device for mechanical cell stimulation and compression in microfluidic settings

Downregulation of GLYAT facilities tumor growth and metastasis and poor clinical outcomes through the PI3K/AKT/Snail pathway in human breast cancer

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