I'm thrilled to announce the publication of my PhD work "Membrane to cortex attachment determines different mechanical phenotypes in LGR5+ and LGR5- colorectal cancer cells"! Find the full paper here: https://t.co/aeOooslW9d. For more insights, check out the thread below. 🎉📚

We’re looking for a passionate PhD fellow to join our #VHIO team in cutting-edge #TranslationalResearch on #biliarytractcancer. Fully funded #FPI fellowship available! visit https://t.co/UcapZjhCP2 #PhD #ScienceJobs #Oncology #cholangiocarcinoma

ENG 🔬 An #IBEC-led study has demonstrated the ability of #ColorectalCancer stem cells to change their mechanical properties, facilitating the successful metastatic process. 🧫 They did this using patient derived tumour #organoids. 👉 Read the news: https://t.co/EfKz2DbZpJ

Special thanks to my amazing lab members for support and ideas during all these years 😍🩷

This is the result of a fantastic collaboration with many great scientists @XavierTrepat @valeria_ventur @adriacanyellas @juanfraam @LeoneRossetti @Ruprecht_Lab @GuckLab @diz_lab and others! Made possible also by all the core facilities at @IBECBarcelona and @PCB_UB !

Our results show that LGR5- cells display a mechanically dynamic phenotype suitable for dissemination from the primary tumor whereas LGR5+ cells display a mechanically stable and resilient phenotype suitable for extravasation and metastatic growth.

And finally, by analyzing single cell RNA-sequencing (scRNA-seq) expression patterns from a patient cohort, we show that this downregulation is a robust signature of colorectal tumors.

By synthetically manipulating the membrane to cortex attachment of LGR5+ cells, we obtain a phenotype similar to the LGR5- cells.

But how can we explain these differences? We found that LGR5+ cells are characterized by a the downregulation of the membrane to cortex attachment proteins Ezrin/Radixin/Moesin (ERMs).

Given the differences in cluster morphology and spreading, we wondered which clusters adhere better to endothelial monolayers and are able to form transendothelial gaps? The answer is LGR5high clusters!

We interpret these results within the biophysical framework of active wetting, finding that LGR5low clusters display contact angles with the substrate close to neutral wetting regime, where velocity is predicted to be maximal.

In a more complex setting, multicellular clusters retain features of single cell behaviorby displaying the same ECM attachment abilities. Additionally, clusters expressing low levels of LGR5 migrate faster and exert less mean traction.

Under confinement, LGR5+ cells respond with higher survival rate and more blebs. However, they move slower compared to the LGR5- cells.

Using a bottom-up approach and patient-derived organoids, we discovered that compared to LGR5- cells, LGR5+ cells are stiffer, adhere better to the ECM and display higher nuclear YAP.

In the context of colorectal cancer heterogeneity and stemness, we wondered: do LGR5+ cancer stem cells differ in their mechanical properties compared to their LGR5- counterparts? And if so, does it change how likely they are to spread?

Are colorectal cancer stem cells mechanically distinct from the rest of the tumor? @SeforaConti addressed this question using patient-derived colorectal cancer organoids. The answer is yes and you can read it in our new preprint (LGR5+ CSCs labelled red) https://t.co/oS5dWfjt7u

The preprint of a great collaboration with @SeforaConti is finally out! Check it out to know more about the mechanical differences of cancer stem cells vs the rest of the tumor, I can ensure for super nice blebs (and much more!)

One of the studies mentioned https://t.co/l1XCQpZP61 showed how identical CVs sent by fake female and male candidates are differently evaluated in favor of the male candidate! A lot to think about..

Incredible talk by @estrade_sonia at #YoungJJESPBBN meeting about the still so bleak situation of gender equality in academia and in Spain in general. No doubt there is still so much to improve!

Incredibly excited to share our article “Metastatic recurrence in colorectal cancer arises from residual EMP1+ cells” published today @Nature. I hope that you like it! A big thank you to all the co-authors for all their hard work! Highlights in the🧵 1/20 https://t.co/FzNv9zCvgg