Matrix stiffness induces an invasive-dormant subpopulation via cGAS-STING axis in oral cancer

Li, Jinyuan; Liu, Yü; Jiang, Hong; Wang, Tao; Li, Kan; Lao, Xiaomei; Liao, Guiqing; Liang, Yujie

doi:10.1016/j.tranon.2023.101681

Cited by 7 publications

(4 citation statements)

References 46 publications

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“…Preventing lymphatic metastasis and post-treatment recurrence in oral squamous cell carcinoma may be achieved by focusing on this mechanism. 186 Through a non-Hippo mechanism, matrix stiffness controls yes-associated protein (YAP) activity through MS. The present study contributes to the growing body of knowledge regarding the biomechanics of cervical cancer by demonstrating that the matrix stiffness of the tumor microenvironment positively regulates EMT in cervical cancer utilizing the yes-associated protein activity via the PPIase non-mitotic a-interaction 1 (Pin1/YAP) pathway.…”

Section: Elasticity Cellular Pathwaysmentioning

confidence: 99%

Cellular elasticity in cancer: a review of altered biomechanical features

Radman,

Alhameed,

Shu

et al. 2024

J. Mater. Chem. B

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Section: Elasticity Cellular Pathwaysmentioning

confidence: 99%

Cellular elasticity in cancer: a review of altered biomechanical features

Radman,

Alhameed,

Shu

et al. 2024

J. Mater. Chem. B

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“…Also, increasing matrix stiffness can cause DNA damage and activate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling. 259 Fibronectin is linked with matrix stiffness in the EMT program via stretching Fibronectin type III through additional growth factors and ECM binding sites. Collagen also works in parallel with fibronectin to increase the tension.…”

Section: Acs Biomaterials Science and Engineeringmentioning

confidence: 99%

“…They found that stiff matrix can cause poor survival, repopulating of tumors, as well as increasing drug resistance and invasiveness based on EMT induction. Also, increasing matrix stiffness can cause DNA damage and activate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling …”

Section: Matrix Stiffness As a Mechanical Modulator Of Tumor Biology ...mentioning

confidence: 99%

Exploiting Matrix Stiffness to Overcome Drug Resistance

Aydin,

Ozcelikkale,

Acar

2024

ACS Biomater. Sci. Eng.

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Drug resistance is arguably one of the biggest challenges facing cancer research today. Understanding the underlying mechanisms of drug resistance in tumor progression and metastasis are essential in developing better treatment modalities. Given the matrix stiffness affecting the mechanotransduction capabilities of cancer cells, characterization of the related signal transduction pathways can provide a better understanding for developing novel therapeutic strategies. In this review, we aimed to summarize the recent advancements in tumor matrix biology in parallel to therapeutic approaches targeting matrix stiffness and its consequences in cellular processes in tumor progression and metastasis. The cellular processes governed by signal transduction pathways and their aberrant activation may result in activating the epithelial-tomesenchymal transition, cancer stemness, and autophagy, which can be attributed to drug resistance. Developing therapeutic strategies to target these cellular processes in cancer biology will offer novel therapeutic approaches to tailor better personalized treatment modalities for clinical studies.

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“… 26 Overall, a stiffened matrix has been correlated with poor survival and post-surgical recurrence in OSCC. 27,28 However, biophysical mechanisms by which stiffening of the ECM drives OSCC progression remain to be determined. Here, we engineered a 3D spheroid culture environment with varying biomechanical properties to study the effect of static matrix stiffness stimuli on mechanosensitive and tumorigenic components in OSCC tumors.…”

Section: Introductionmentioning

confidence: 99%

Three-dimensional matrix stiffness modulates mechanosensitive and phenotypic alterations in oral squamous cell carcinoma spheroids

Sheth,

Sharma,

Lehn

et al. 2024

APL Bioengineering

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Extracellular biophysical cues such as matrix stiffness are key stimuli tuning cell fate and affecting tumor progression in vivo. However, it remains unclear how cancer spheroids in a 3D microenvironment perceive matrix mechanical stiffness stimuli and translate them into intracellular signals driving progression. Mechanosensitive Piezo1 and TRPV4 ion channels, upregulated in many malignancies, are major transducers of such physical stimuli into biochemical responses. Most mechanotransduction studies probing the reception of changing stiffness cues by cells are, however, still limited to 2D culture systems or cell-extracellular matrix models, which lack the major cell–cell interactions prevalent in 3D cancer tumors. Here, we engineered a 3D spheroid culture environment with varying mechanobiological properties to study the effect of static matrix stiffness stimuli on mechanosensitive and malignant phenotypes in oral squamous cell carcinoma spheroids. We find that spheroid growth is enhanced when cultured in stiff extracellular matrix. We show that the protein expression of mechanoreceptor Piezo1 and stemness marker CD44 is upregulated in stiff matrix. We also report the upregulation of a selection of genes with associations to mechanoreception, ion channel transport, extracellular matrix organization, and tumorigenic phenotypes in stiff matrix spheroids. Together, our results indicate that cancer cells in 3D spheroids utilize mechanosensitive ion channels Piezo1 and TRPV4 as means to sense changes in static extracellular matrix stiffness, and that stiffness drives pro-tumorigenic phenotypes in oral squamous cell carcinoma.

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Matrix stiffness induces an invasive-dormant subpopulation via cGAS-STING axis in oral cancer

Cited by 7 publications

References 46 publications

Cellular elasticity in cancer: a review of altered biomechanical features

Cellular elasticity in cancer: a review of altered biomechanical features

Exploiting Matrix Stiffness to Overcome Drug Resistance

Three-dimensional matrix stiffness modulates mechanosensitive and phenotypic alterations in oral squamous cell carcinoma spheroids

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