RNA interference screens discover proteases as synthetic lethal partners of PI3K inhibition in breast cancer cells.

ABSTRACT:

Rationale

PI3K/mTOR signaling is frequently upregulated in breast cancer making inhibitors of this pathway highly promising anticancer drugs. However, PI3K-inhibitors have a low therapeutic index. Therefore, finding novel combinatory treatment options represents an important step towards clinical implementation of PI3K pathway inhibition in breast cancer therapy. Here, we propose proteases as potential synergistic partners with simultaneous PI3K inhibition in breast cancer cells.

Methods

We performed mRNA expression studies and unbiased functional genetic synthetic lethality screens by a miR-E based knockdown system targeting all genome-encoded proteases, i.e. the degradome of breast cancer cells. Importantly theses RNA interference screens were done in combination with two

SUBMITTER: Holzen L 

PROVIDER: S-EPMC9169373 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature