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FIGURE 2 from Genome-wide CRISPR Screen Reveals RAB10 as a Synthetic Lethal Gene in Colorectal and Pancreatic Cancers Carrying SMAD4 Loss

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posted on 2023-05-04, 14:20 authored by Hélène Erasimus, Vanessa Kolnik, Frédéric Lacroix, Sukhvinder Sidhu, Stéphane D'Agostino, Olivier Lemaitre, Alexandre Rohaut, Isabelle Sanchez, Gilbert Thill, Michel Didier, Laurent Debussche, Christophe Marcireau

SMAD4-inducible restoration restores the TGFβ-induced growth inhibition of colorectal cancer cells in vivo.A,In vivo tumorigenicity assay. To assess the effects of SMAD4 restoration in SMAD4-deficient cell lines on tumorigenicity, parental cell line as well as clones stably expressing a doxycycline-inducible Smad4 were injected subcutaneously into the flank region of female SCID mice. Tumor volume over time is plotted. Square: no treatment; Triangle: Glucose treatment; Circle: Doxycycline treatment. Mean with SD (ns, P > 0.05; *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001). B, At the end of the experiment, SMAD4-reexpressing HT29 tumors were harvested, frozen and a protein extraction was performed to assess the level of SMAD4 by Western blot analysis.

Funding

Sanofi (Sanofi US)

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ARTICLE ABSTRACT

This study identified and validated RAB10 as new synthetic lethal gene with SMAD4. This was achieved by conducting a whole-genome CRISPR screens in different colorectal and pancreatic cell lines. A future RAB10 inhibitors could correspond to a new therapeutic solution for patients with cancer with SMAD4 deletion.