American Association for Cancer Research
crc-22-0301_fig2.png (318.65 kB)

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.


Sanofi (Sanofi US)



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.