Back

LSD1 promotes secretory cell specification to drive BRAF mutant colorectal cancer

Miller, S. A.; Policastro, R. A.; Sriramkumar, S.; Lai, T.; Huntington, T. D.; Ladaika, C. A.; Zentner, G. E.; O'Hagan, H. M.

2020-09-25 cancer biology
10.1101/2020.09.25.313536 bioRxiv
Show abstract

Despite the connection to distinct mucus-containing colorectal cancer (CRC) histological subtypes, the role of secretory cells, including goblet and enteroendocrine (EEC) cells, in CRC progression has been underexplored. Analysis of TCGA and single cell RNA sequencing data demonstrates that multiple secretory progenitor populations are enriched in BRAF-mutant CRC patient tumors and cell lines. Enrichment of EEC progenitors in BRAF-mutant CRC is maintained by DNA methylation and silencing of NEUROD1, a key gene required for differentiation of EECs. Mechanistically, secretory cells and the factors they secrete, such as Trefoil factor 3, are shown to promote colony formation and activation of cell survival pathways in the entire cell population. We further identify LSD1 as a critical regulator of secretory cell specification in vitro and in a colon orthotopic xenograft model, where LSD1 loss reduces tumor growth and metastasis. This work establishes EEC progenitors, in addition to goblet cells, as targetable populations in BRAF-mutant CRC and identifies LSD1 as a therapeutic target in secretory lineage-containing CRC.

Matching journals

The top 5 journals account for 50% of the predicted probability mass.

1
eLife
● 5828 papers in training set
Top 2%
19.1%
Similar papers in this journal
2
Cellular and Molecular Gastroenterology and Hepatology
○ 46 papers in training set
Top 0.1%
13.4%
Similar papers in this journal
3
Cell Reports
○ 1498 papers in training set
Top 1%
12.3%
Similar papers in this journal
4
JCI Insight
● 277 papers in training set
Top 2%
3.3%
Similar papers in this journal
5
Molecular Cancer Research
● 49 papers in training set
Top 0.4%
2.9%
Similar papers in this journal
50% of probability mass above
6
Nature Communications
○ 5641 papers in training set
Top 39%
2.5%
7
Cancers
○ 213 papers in training set
Top 2%
2.2%
8
Gastroenterology
○ 42 papers in training set
Top 0.4%
2.2%
9
Cancer Research Communications
● 51 papers in training set
Top 0.8%
1.8%
10
Disease Models & Mechanisms
139 papers in training set
Top 1%
1.8%
11
Biology Open
● 156 papers in training set
Top 2%
1.5%
12
Life Science Alliance
● 285 papers in training set
Top 4%
1.5%
13
Cancer Cell
○ 42 papers in training set
Top 0.9%
1.4%
14
PLOS Genetics
● 862 papers in training set
Top 8%
1.4%
15
iScience
○ 1154 papers in training set
Top 23%
1.4%
16
Journal of Experimental Medicine
● 119 papers in training set
Top 2%
1.2%
17
Gastro Hep Advances
○ 11 papers in training set
Top 0.2%
1.2%
18
Scientific Reports
○ 3612 papers in training set
Top 61%
1.2%
19
Cancer Research
● 130 papers in training set
Top 2%
1.2%
20
NAR Cancer
◐ 37 papers in training set
Top 0.6%
1.1%
21
Communications Biology
○ 993 papers in training set
Top 24%
1.1%
22
Journal of Biological Chemistry
○ 690 papers in training set
Top 8%
1.1%
23
Molecular Biology of the Cell
● 311 papers in training set
Top 3%
0.9%
24
Molecular Cancer
○ 16 papers in training set
Top 0.3%
0.9%
25
Developmental Cell
○ 196 papers in training set
Top 4%
0.9%
26
Genes & Development
● 90 papers in training set
Top 2%
0.9%
27
Cell Reports Medicine
○ 153 papers in training set
Top 4%
0.9%
28
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 40%
0.9%
29
EMBO Reports
○ 263 papers in training set
Top 6%
0.9%
30
Science Advances
● 1243 papers in training set
Top 32%
0.6%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.