Evidence map›Paper›PMID 37327088›Full record

ArticleJournal of molecular cell biology2023

A targetable pathway to eliminate TRA-1-60+/TRA-1-81+ chemoresistant cancer cells.

Lei Tan, Xiaohua Duan, Pratyusha Mutyala, Ting Zhou, Sadaf Amin, Tuo Zhang, Brian Herbst, Gokce Askan, Tomer Itkin, Zhaoying Xiang and 6 more

Open access · goldAbstract read
In one paragraph

Article in Journal of molecular cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.1field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 2 countries.

Lei TanDepartment of Surgery, Weill Cornell Medicine, New York, NY 10065, USA.
Xiaohua DuanDepartment of Surgery, Weill Cornell Medicine, New York, NY 10065, USA.
Pratyusha MutyalaDepartment of Surgery, Weill Cornell Medicine, New York, NY 10065, USA.
Ting ZhouThe SKI Stem Cell Research Facility, The Center for Stem Cell Biology and Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Sadaf AminDepartment of Surgery, Weill Cornell Medicine, New York, NY 10065, USA.
Tuo ZhangGenomic Resource Core Facility, Weill Cornell Medical College, New York, NY 10065, USA.
Brian HerbstRubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Gokce AskanRubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Tomer ItkinDivision of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
Zhaoying XiangGenomic Resource Core Facility, Weill Cornell Medical College, New York, NY 10065, USA.
Fabrizio MichelassiDepartment of Surgery, Weill Cornell Medicine, New York, NY 10065, USA.
Michael D LiebermanDepartment of Surgery, Weill Cornell Medicine, New York, NY 10065, USA.
Christine A Iacobuzio-DonahueRubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Steven D LeachDartmouth Cancer Center, Darmouth College, Hanover, NH 03755, USA.
Todd EvansDepartment of Surgery, Weill Cornell Medicine, New York, NY 10065, USA.
Shuibing ChenDepartment of Surgery, Weill Cornell Medicine, New York, NY 10065, USA.ORCID 0000-0002-6294-5187
Cornell University · USMemorial Sloan Kettering Cancer Center · USChinese Academy of Sciences · CNDartmouth College · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Comprehensive genetic dissection of druggable KRAS targetsR01CA204228 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI LEACH, STEVEN D · 2016 to 2020
$1.9M
NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA204228NIH HHS R01 CA204228
6 · The paper itself

Abstract

Chemoresistance is a primary cause of treatment failure in pancreatic cancer. Identifying cell surface markers specifically expressed in chemoresistant cancer cells (CCCs) could facilitate targeted therapies to overcome chemoresistance. We performed an antibody-based screen and found that TRA-1-60 and TRA-1-81, two 'stemness' cell surface markers, are highly enriched in CCCs. Furthermore, TRA-1-60+/TRA-1-81+ cells are chemoresistant compared to TRA-1-60-/TRA-1-81- cells. Transcriptome profiling identified UGT1A10, shown to be both necessary and sufficient to maintain TRA-1-60/TRA-1-81 expression and chemoresistance. From a high-content chemical screen, we identified Cymarin, which downregulates UGT1A10, eliminates TRA-1-60/TRA-1-81 expression, and increases chemosensitivity both in vitro and in vivo. Finally, TRA-1-60/TRA-1-81 expression is highly specific in primary cancer tissue and positively correlated with chemoresistance and short survival, which highlights their potentiality for targeted therapy. Therefore, we discovered a novel CCC surface marker regulated by a pathway that promotes chemoresistance, as well as a leading drug candidate to target this pathway.

Indexed as

Drug Resistance, NeoplasmPancreatic NeoplasmsCell Line, TumorGene Expression ProfilingHumanschemoresistanceCymarinpancreatic cancerTRA-1-60/TRA-1-81UGT1A10

Identifiers

PMID37327088
PMCPMC10847630
OpenAlexW4380992388

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.