Linking E-cadherin mechanotransduction to cell metabolism through force-mediated activation of AMPK

Bays, Jennifer; Campbell, Hannah; Heidema, Christy; Sebbagh, Michaël; DeMali, Kris A.

doi:10.1038/ncb3537

Cited by 191 publications

(210 citation statements)

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“…Increasing evidences suggest a central connection of mechanotransduction – including the YAP/TAZ pathway – with cellular metabolism (Santinon et al, 2018; Yang et al, 2018), and processes related to glucose consumption and Warburg metabolism (Bays et al, 2017; Enzo et al, 2015; Mo et al, 2015; Sorrentino et al, 2014; Wang et al, 2015). However, increased glycolysis alone is insufficient to meet the total metabolic demands of proliferating cells.…”

Section: Introductionmentioning

confidence: 99%

Tumor-Stroma Mechanics Coordinate Amino Acid Availability to Sustain Tumor Growth and Malignancy

et al. 2019

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Summary Dysregulation of extracellular matrix (ECM) deposition and cellular metabolism promotes tumor aggressiveness by sustaining the activity of key growth, invasion, and survival pathways. Yet, mechanisms by which biophysical properties of ECM relate to metabolic processes and tumor progression remain undefined. In both cancer cells and carcinomaassociated fibroblasts (CAF), we found that ECM stiffening mechanoactivates glycolysis and glutamine metabolism and thus coordinates non-essential amino acid flux within the tumor niche. Specifically, we demonstrate a metabolic crosstalk between CAF and cancer cells in which CAF-derived aspartate sustains cancer cell proliferation, while cancer cell-derived glutamate balances the redox state of CAF to promote ECM remodeling. Collectively, our findings link mechanical stimuli to dysregulated tumor metabolism and thereby highlight a new metabolic network within tumors in which diverse fuel sources are used to promote growth and aggressiveness. Furthermore, this study identifies potential metabolic drug targets for therapeutic development in cancer.

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Section: Introductionmentioning

confidence: 99%

Tumor-Stroma Mechanics Coordinate Amino Acid Availability to Sustain Tumor Growth and Malignancy

et al. 2019

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“…2 Application of force increases co-localization and co-immunoprecipitation of LKB1 with E-cadherin. 1 When LKB1 is inhibited, forceinduced AMPK activation and recruitment to the cadherins is blocked. Hence, LKB1 mediates AMPK recruitment and activation at cell-cell contacts.…”

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confidence: 99%

“…4,5 Our studies reveal a 2.0-fold increase in E-cadherin deposition in cell-cell junctions and a 3.8-fold increase in junctional actin. 1 Cells require both AMPK and increased ATP production to support the cytoskeletal changes necessary for cell stiffening. Hence, not only does forceinduced AMPK stimulate glucose uptake and increased contractility, but also the energy is used to support elevated tension.…”

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confidence: 99%

“…In response to force on E-cadherin, we observe increased glucose uptake in 2 cell lines in response to multiple forces. 1 The glucose uptake requires increased contractility and E-cadherin expression. Also of note, the glucose taken up into the cell was converted to ATP.…”

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confidence: 99%

“…1 Specifically, application of shear stress or tensile force to E-cadherin on 2 different epithelial cell lines triggers activation of AMP-dependent kinase (AMPK, Fig. 1).…”

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confidence: 99%

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Unraveling the Mechanobiology Underlying Traumatic Brain Injury with Advanced Technologies and Biomaterials

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Traumatic brain injury (TBI) is a worldwide health and socioeconomic problem, associated with prolonged and complex neurological aftermaths, including a variety of functional deficits and neurodegenerative disorders. Research on the long-term effects has highlighted that TBI shall be regarded as a chronic health condition. The initiation and exacerbation of TBI involve a series of mechanical stimulations and perturbations, accompanied by mechanotransduction events within the brain tissues. Mechanobiology thus offers a unique perspective and likely promising approach to unravel the underlying molecular and biochemical mechanisms leading to neural cells dysfunction after TBI, which may contribute to the discovery of novel targets for future clinical treatment. This article investigates TBI and the subsequent brain dysfunction from a lens of neuromechanobiology. Following an introduction, the mechanobiological insights are examined into the molecular pathology of TBI, and then an overview is given of the latest research technologies to explore neuromechanobiology, with particular focus on microfluidics and biomaterials. Challenges and prospects in the current field are also discussed. Through this article, it is hoped that extensive technical innovation in biomedical devices and materials can be encouraged to advance the field of neuromechanobiology, paving potential ways for the research and rehabilitation of neurotrauma and neurological diseases.

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Linking E-cadherin mechanotransduction to cell metabolism through force-mediated activation of AMPK

Cited by 191 publications

References 47 publications

Tumor-Stroma Mechanics Coordinate Amino Acid Availability to Sustain Tumor Growth and Malignancy

Tumor-Stroma Mechanics Coordinate Amino Acid Availability to Sustain Tumor Growth and Malignancy

It takes energy to resist force

Unraveling the Mechanobiology Underlying Traumatic Brain Injury with Advanced Technologies and Biomaterials

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