DOI: 10.5061/dryad.rbnzs7hq6
title: Liver regeneration-associated hepatocellular YAP1 activation prevents colorectal cancer liver metastasis through glutamine competition

description: Literature suggests that hepatocellular Yes-associated Protein 1 (YAP1)
 signaling is activated following hepatectomy, and that such activation can
 suppress the growth of metastatic liver tumors. This study aims to explore
 the mechanisms by which surgical techniques influence colorectal cancer
 liver metastasis (CRLM). The prognosis of a real-world cohort of 240 CRLM
 patients undergoing major and minor hepatectomy was compared after
 adjusting for confounders. To model CRLM, we induced liver metastasis in
 mice by transsplenically injecting MC38 cells. Cytometry by
 Time-Of-Flight, RNA sequencing, and untargeted metabolomics were used to
 explore how surgical choice affected CRLM prognosis. IHC was performed in
 another real-world cohort of 150 CRLM patients treated with hepatectomy to
 confirm the role of YAP1 signaling in CRLM progression. We found that CRLM
 patients and mice undergoing major hepatectomy had longer survival and
 lower recurrence rates compared to those undergoing minor hepatectomy.
 Mechanistically, extensive hepatectomy activated hepatocellular YAP1 by
 regulating epidermal growth factor receptor, altering glutamine metabolism
 genes, and increasing liver glutamine consumption. This metabolic shift
 led to glutamine scarcity in tumor cells, causing higher reactive oxygen
 species production, which inhibited YAP1 activity in tumor cells.
 Consequently, chemokine C-X-C motif chemokine ligand 5 (CXCL5) production
 decreased, reducing myeloid-derived suppressor cells (MDSCs) infiltration
 and enhancing CD8+ T cell immunological function. We propose that major
 hepatectomy may upregulate hepatocellular YAP1 activity while
 downregulating tumoral YAP1 activation through glutamine competition,
 which leads to reduced MDSCs infiltration in the tumor, thereby
 suppressing the growth and recurrence of CRLM.
description: # Liver regeneration-associated hepatocellular YAP1 activation prevents
 colorectal cancer liver metastasis through glutamine competition Dataset
 DOI: [10.5061/dryad.rbnzs7hq6 ](10.5061/dryad.rbnzs7hq6) ## Description of
 the data and file structure RNA sequencing data included in the manuscript
 "Liver regeneration-associated hepatocellular YAP1 activation
 prevents colorectal cancer liver metastasis through glutamine
 competition". ### Files and variables #### File:
 Liver_sham_vs_minor_vs_major.csv **Description:** RNA sequencing data for
 Figure 2B in the manuscript "Liver regeneration-associated
 hepatocellular YAP1 activation prevents colorectal cancer liver metastasis
 through glutamine competition". ##### Variables * Name: Gene symbols
 * LR0_1:fpkm: Liver tissue of mice 3 days after sham-operation, replicate
 1. * LR0_2:fpkm:  Liver tissue of mice 3 days after sham-operation,
 replicate 2. * LR0_3:fpkm:  Liver tissue of mice 3 days after
 sham-operation, replicate 3. * LR30_1:fpkm: Liver tissue of mice 3 days
 post 30% partial hepatectomy, replicate 1.  * LR30_2:fpkm:  Liver tissue
 of mice 3 days post 30% partial hepatectomy, replicate 2. * LR30_3:fpkm: 
 Liver tissue of mice 3 days post 30% partial hepatectomy, replicate 3. *
 LR70_1:fpkm:  Liver tissue of mice 3 days post 70% partial hepatectomy,
 replicate 1. * LR70_2:fpkm:  Liver tissue of mice 3 days post 70% partial
 hepatectomy, replicate 2. * LR70_3:fpkm:  Liver tissue of mice 3 days post
 70% partial hepatectomy, replicate 3. #### File: tumor_sham_vs_PHx.csv
 **Description:** RNA sequencing data for Figure 4A in the manuscript
 "Liver regeneration-associated hepatocellular YAP1 activation
 prevents colorectal cancer liver metastasis through glutamine
 competition". ##### Variables * gene_symbol: Gene symbols *
 sham1: Tumor tissue of CRLM mice 4 weeks after sham-operation, replicate
 1. * sham2: Tumor tissue of CRLM mice 4 weeks after sham-operation,
 replicate 2. * sham3: Tumor tissue of CRLM mice 4 weeks after
 sham-operation, replicate 3. * PHx1: Tumor tissue of CRLM mice 4 weeks
 after 70% liver resection, replicate 1. * PHx2: Tumor tissue of CRLM mice
 4 weeks after 70% liver resection, replicate 2. * PHx3: Tumor tissue of
 CRLM mice 4 weeks after 70% liver resection, replicate 3. ## Code/software
 MS Excel can be used to view the files ## Access information Other
 publicly accessible locations of the data: * Not applicable. Data was
 derived from the following sources: * Not applicable.