PT  - JOURNAL ARTICLE
AU  - M. Di-Luoffo
AU  - M. Delarue
AU  - J. Guillermet-Guibert
TI  - The biomechanical context influences the output signaling, independently of <em>PIK3CA</em> mutations in breast cancer cells
AID  - 10.1101/2021.10.18.464825
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.10.18.464825
4099  - http://biorxiv.org/content/early/2021/10/19/2021.10.18.464825.short
4100  - http://biorxiv.org/content/early/2021/10/19/2021.10.18.464825.full
AB  - Mechanical stresses including tensile and compressive stresses are ubiquitous in nature, and are now well-recognized as being inherent to the development of most cancers. They are integrated by mechanotransduction in cells. Tensile stress is largely associated with YAP/TAZ pathway activation. However, less is known about signaling induced by compressive stress, the latter arising from extracellular matrix remodeling and local tumor growth. In the present study, we used transcriptomic data obtained after unidirectional compression of wildtype and mutant PIK3CA breast cancer cells from Kim et al., 2019. We analyzed in an unbiased manner signatures of cell signaling activation including phosphoinositide 3-kinases (PI3Ks) activity pathway in response to compressive stress. Because we found that PI3K activation occurred upon compression, we studied PI3K isoform-specific pathways using known transcriptional targets of PI3Kα inhibitor (BYL719) or of PI3Kβ inhibitor (AZD8186). Our study provides transcriptomic evidences for the role of PI3K pathway in compression-induced mechanotransduction, through the roles of isoform-specific class I PI3Ks and independently of PIK3CA alterations. In a compressive environment, the canonical pathways (YAP/TAZ and Piezo) was not increased, while other targetable mechanisms, such as PI3K signal or autophagy, may provide a proliferative advantage and increased cell resistance to chemotherapies.Competing Interest StatementThe authors have declared no competing interest.