🥳I am beyond to finally share the story of my PhD out now: USP10 drives cancer stemness and enables super-competitor signalling in colorectal cancer Lets have a little look what we found: 🧵1/11.

RT @DikicLab: Excited to share our latest research published in @ScienceMagazine! Cryptic splicing can lead to proteotoxic stress, but how….

And last but not least – the biggest shout out to my PhD supervisor and mentor Markus and the whole @DiefenbacherL! None of this would have been possible without your help and support! 11/11.

Special thanks to.@JeroenBugter and @MadelonMaurice.@sinah_loebbert and @Daniel_Solvie.@CristianPG_mlg and the @DikicLab.@SchulteClemens and @maric_hans.@_WolfLab, Peter Gallant and @amir_orian and many many others! 10/11.

Thank you to everyone involved in this highly collaborative effort spanning all kinds of different expertise! It would not have been possible without you all 🙏🐭🪰👩‍🔬🥼 9/11.

With the combined forces of so many great collaborators and by performing various in vitro and in vivo experiments, we were able to show that USP10 acts as an APC truncation-specific regulator of b-catenin in CRC, thereby contributing to tumour initiation and maintenance! 8/11

Identification of this fascinating APC-truncation specific mechanism now raised the question for USP10 as potential new therapeutic target – and indeed, shRNA-mediated KD of USP10 in patient-derived APC-trunc CRC organoids led to a strong decrease in size🥳 7/11

Since WNT signalling is also highly conserved in flies, we were curious about USP10s role in Drosophila. And what we found was super cool - depletion of USP10 in an APC-driven hyperplasia model almost completely restored survival of APC-truncated flies. 6/11

In all of our model systems, we looked at a specific short APC truncation, so we wondered if this interaction was actually enabled by a specific APC truncation mutation. And by doing in vitro interaction experiments, we were able to demonstrate this mechanism very nicely. 5/11

Not only did we find that USP10 is upregulated in humans, but this observation was also conserved in different mouse models of CRC. Interestingly, using CRISPR-engineered mouse SI organoids, we were also able to show that USP10 is upregulated upon transformation. 4/11

To answer this, we performed an siRNA DUB-library screen and identified USP10 as novel regulator of b-Catenin stability in APC-mutant HT-29 cells. Interestingly USP10 is also highly upregulated in CRC patients and correlated with poor survival. 3/11

Mutations in WNT signalling pathway account for about 80% of CRC cases, mainly by stabilising b-Catenin. However, when we analysed b-Catenin ubiquitylation in various CRC-derived cell lines it was still ubiquitylated – so why does it not get degraded? 2/11

RT @DiefenbacherL: 🚨 Check our latest paper in Oncogen! By combining #proteomics, #spatialtranscriptomics #AlphaFold #organoids and innova….

RT @oncogenejournal: USP10 emerges as a unique therapeutic target in APC-truncated #ColorectalCancer. 🔬 @Diefenbach….

RT @_WolfLab: We congratulate Michaela Reissland and the whole team in Markus Diefenbacher's lab on their new paper in Oncogene. In the stu….

So proud of my first first-author paper🥳Can´t be more grateful to all who contributed wrapping up my PhD project to this great story! Little thread about our most important finding will follow soon🧵.

RT @bulutkarslioglu: Our PhD program is now open to applications for 2025 admissions. Too much cool science to summarize, take a look and a….

@ATCC_LGC @SigmaAldrich And please RT - to increase my chances of finding an alternative supplier🙏.

Neither @ATCC_LGC nor @SigmaAldrich were able to deliver the ones, we´ve ordered so far to germany (just needed >4 month to figure that out. 🙄).

👋#science twitter - help needed! We are desperately looking for commercially available CRC-patient organoid lines and normal colon organoids. Any recommendations other than Atcc or Sigma? #organoids #CancerResearch.