Next Article in Journal
Genomic Abnormalities as Biomarkers and Therapeutic Targets in Acute Myeloid Leukemia
Next Article in Special Issue
The Clinical and Theranostic Values of Activated Leukocyte Cell Adhesion Molecule (ALCAM)/CD166 in Human Solid Cancers
Previous Article in Journal
Copy Neutral LOH Affecting the Entire Chromosome 6 Is a Frequent Mechanism of HLA Class I Alterations in Cancer
Previous Article in Special Issue
SIPA1 Is a Modulator of HGF/MET Induced Tumour Metastasis via the Regulation of Tight Junction-Based Cell to Cell Barrier Function
Article

E-Cadherin Regulates Mitochondrial Membrane Potential in Cancer Cells

1
Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA
2
USC Stem Cell, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
3
Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Tracey Martin and Andrew Sanders
Cancers 2021, 13(20), 5054; https://doi.org/10.3390/cancers13205054
Received: 30 August 2021 / Revised: 4 October 2021 / Accepted: 5 October 2021 / Published: 9 October 2021
(This article belongs to the Special Issue Cell Adhesion Molecules in Metastasis)
Cancer cells have unusually high mitochondrial membrane potential (ΔΨm). However, the microenvironmental mechanisms that regulate cancer cell ΔΨm remain unclear. In this study, we use in vitro micropatterned tumor models to mimic the confinement cues in tumor microenvironments and show that the E-cadherin mediated intercellular adhesion negatively regulates cancer cell ΔΨm.
Epithelial cancer cells often have unusually higher mitochondrial membrane potential (ΔΨm) than their normal counterparts, which has been associated with increased invasiveness in vitro and higher metastatic potential in vivo. However, the mechanisms by which ΔΨm in cancer cells is regulated in tumor microenvironment (TME) remain unclear. In this study, we used an in vitro micropatterning platform to recapitulate biophysical confinement cues in the TME and investigated the mechanisms by which these regulate cancer cell ΔΨm. We found that micropatterning resulted in a spatial distribution of ΔΨm, which correlated with the level of E-cadherin mediated intercellular adhesion. There was a stark contrast in the spatial distribution of ΔΨm in the micropattern of E-cadherin-negative breast cancer cells (MDA-MB-231) compared to that of the high E-cadherin expressing (MCF-7) cancer cells. Disruption and knockout of E-cadherin adhesions rescued the low ΔΨm found at the center of MCF-7 micropatterns with high E-cadherin expression, while E-cadherin overexpression in MDA-MB-231 and MCF-7 cells lowered their ΔΨm at the micropattern center. These results show that E-cadherin plays an important role in regulating the ΔΨm of cancer cells in the context of biophysical cues in TME. View Full-Text
Keywords: mitochondrial membrane potential; tumor microenvironment; E-cadherin; adherens junction; MCF-7; MDA-MB-231; CRISPR/Cas9; breast cancer mitochondrial membrane potential; tumor microenvironment; E-cadherin; adherens junction; MCF-7; MDA-MB-231; CRISPR/Cas9; breast cancer
Show Figures

Figure 1

MDPI and ACS Style

Begum, H.M.; Mariano, C.; Zhou, H.; Shen, K. E-Cadherin Regulates Mitochondrial Membrane Potential in Cancer Cells. Cancers 2021, 13, 5054. https://doi.org/10.3390/cancers13205054

AMA Style

Begum HM, Mariano C, Zhou H, Shen K. E-Cadherin Regulates Mitochondrial Membrane Potential in Cancer Cells. Cancers. 2021; 13(20):5054. https://doi.org/10.3390/cancers13205054

Chicago/Turabian Style

Begum, Hydari M., Chelsea Mariano, Hao Zhou, and Keyue Shen. 2021. "E-Cadherin Regulates Mitochondrial Membrane Potential in Cancer Cells" Cancers 13, no. 20: 5054. https://doi.org/10.3390/cancers13205054

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop