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Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression
- Mouw, Janna K;
- Yui, Yoshihiro;
- Damiano, Laura;
- Bainer, Russell O;
- Lakins, Johnathon N;
- Acerbi, Irene;
- Ou, Guanqing;
- Wijekoon, Amanda C;
- Levental, Kandice R;
- Gilbert, Penney M;
- Hwang, E Shelley;
- Chen, Yunn-Yi;
- Weaver, Valerie M
Abstract
Mouw et al. delineate a molecular pathway by which matrix stiffness promotes tumor malignancy. Upon matrix stiffening, integrin signaling is engaged, triggering a signaling cascade that regulates the protumorigenic microRNA miR-18a. This leads to downregulation of PTEN and activation of oncogenic signaling. The pathway provides a link between mechanotransduction, miR regulation and oncogene activation that integrates biophysical changes into tumor progression and can also be altered in human tumors.
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