@article {67298, title = {Adhesion-mediated mechanosignaling forces mitohormesis.}, journal = {Cell Metabolism}, volume = {33}, year = {2021}, month = {2021 July 6}, pages = {1322}, abstract = {

Mitochondria control eukaryotic cell fate by producing the energy needed to support life and the signals required to execute programed cell death. The biochemical milieu is known to affect mitochondrial function and contribute to the dysfunctional mitochondrial phenotypes implicated in cancer and the morbidities of aging. However, the physical characteristics of the extracellular matrix are also altered in cancerous and aging tissues. Here, we demonstrate that cells sense the physical properties of the extracellular matrix and activate a mitochondrial stress response that adaptively tunes mitochondrial function via solute carrier family 9 member A1-dependent ion exchange and heat shock factor 1-dependent transcription. Overall, our data indicate that adhesion-mediated mechanosignaling may play an unappreciated role in the altered mitochondrial functions observed in aging and cancer.

}, issn = {1932-7420}, doi = {10.1016/j.cmet.2021.04.017}, author = {Tharp, Kevin M and Higuchi-Sanabria, Ryo and Timblin, Greg A and Ford, Breanna and Garzon-Coral, Carlos and Schneider, Catherine and Muncie, Jonathon M and Stashko, Connor and Daniele, Joseph R and Moore, Andrew S and Frankino, Phillip A and Homentcovschi, Stefan and Manoli, Sagar S and Shao, Hao and Richards, Alicia L and Chen, Kuei-Ho and Hoeve, Johanna Ten and Ku, Gregory M and Hellerstein, Marc and Nomura, Daniel K and Saijo, Karou and Gestwicki, Jason and Dunn, Alexander R and Krogan, Nevan J and Swaney, Danielle L and Dillin, Andrew and Weaver, Valerie M} } @article {65894, title = {A bulky glycocalyx fosters metastasis formation by promoting G1 cell cycle progression}, journal = {eLife}, volume = {6}, year = {2017}, month = {Sep-12-2018}, abstract = {

Metastasis depends upon cancer cell growth and survival within the metastatic niche. Tumors which remodel their glycocalyces, by overexpressing bulky glycoproteins like mucins, exhibit a higher predisposition to metastasize, but the role of mucins in oncogenesis remains poorly understood. Here we report that a bulky glycocalyx promotes the expansion of disseminated tumor cells in vivo by fostering integrin adhesion assembly to permit G1 cell cycle progression. We engineered tumor cells to display glycocalyces of various thicknesses by coating them with synthetic mucin-mimetic glycopolymers. Cells adorned with longer glycopolymers showed increased metastatic potential, enhanced cell cycle progression, and greater levels of integrin-FAK mechanosignaling and Akt signaling in a syngeneic mouse model of metastasis. These effects were mirrored by expression of the ectodomain of cancer-associated mucin MUC1. These findings functionally link mucinous proteins with tumor aggression, and offer a new view of the cancer glycocalyx as a major driver of disease progression.

}, doi = {https://doi.org/10.7554/eLife.25752}, url = {https://elifesciences.org/articles/25752}, author = {Woods, Elliot C and Kai, FuiBoon and Barnes, J Matthew and Pedram, Kayvon and Pickup, Michael W and Hollander, Michael J and Weaver, Valerie M and Bertozzi, Carolyn R} } @article {48496, title = {Visualizing dynamic microvillar search and stabilization during ligand detection by T cells.}, journal = {Science (New York, N.Y.)}, volume = {356}, year = {2017}, month = {2017 May 12}, abstract = {

During immune surveillance, T cells survey the surface of antigen-presenting cells. In searching for peptide-loaded major histocompatibility complexes (pMHCs), they must solve a classic trade-off between speed and sensitivity. It has long been supposed that microvilli on T cells act as sensory organs to enable search, but their strategy has been unknown. We used lattice light-sheet and quantum dot-enabled synaptic contact mapping microscopy to show that anomalous diffusion and fractal organization of microvilli survey the majority of opposing surfaces within 1 minute. Individual dwell times were long enough to discriminate pMHC half-lives and T cell receptor (TCR) accumulation selectively stabilized microvilli. Stabilization was independent of tyrosine kinase signaling and the actin cytoskeleton, suggesting selection for avid TCR microclusters. This work defines the efficient cellular search process against which ligand detection takes place.

}, issn = {1095-9203}, doi = {10.1126/science.aal3118}, author = {Cai, En and Marchuk, Kyle and Beemiller, Peter and Beppler, Casey and Rubashkin, Matthew G and Weaver, Valerie M and G{\'e}rard, Audrey and Liu, Tsung-Li and Chen, Bi-Chang and Betzig, Eric and Bartumeus, Frederic and Krummel, Matthew F} }