Evidence map›Paper›PMID 35688945›Full record

ArticleOncogene2022

Addiction of Merkel cell carcinoma to MUC1-C identifies a potential new target for treatment.

Yoshihiro Morimoto, Atsushi Fushimi, Nami Yamashita, Masayuki Hagiwara, Atrayee Bhattacharya, Jingwei Cheng, Thomas C Frost, Rehan Ahmad, Tatsuaki Daimon, Lei Huang and 6 more

Open access · hybridAbstract read
In one paragraph

Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.8field-weighted citation impact, top 13% 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

14 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. MUC1-C Is a Common Driver of Acquired Osimertinib Resistance in NSCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2024
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Dependence on MUC1-C in Progression of Neuroendocrine Prostate Cancer.International journal of molecular sciences · 2023
    Review
  13. Article
  14. Emergence ofCancers · 2022
    Review
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 2 institutions in 3 countries.

Yoshihiro MorimotoDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Atsushi FushimiDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Nami YamashitaDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Masayuki HagiwaraDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Atrayee BhattacharyaDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Jingwei ChengDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Thomas C FrostDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Rehan AhmadDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Tatsuaki DaimonDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Lei HuangDepartment of Histoembryology, Genetics and Developmental Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Key Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
Tsuyoshi HataDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Hidekazu TakahashiDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Masaaki YamamotoDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Yozo SuzukiDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-4567-3802
James A DeCaprioDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-0896-167X
Donald KufeDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. donald_kufe@dfci.harvard.edu.ORCID 0000-0001-5743-8888
Harvard University · USShanghai Jiao Tong University · CN

Funding

Targeting the MUC1-C Oncoprotein in Triple-Negative Breast CancerR01CA097098 · NCI · DANA-FARBER CANCER INSTITUTE · PI DONALD W. KUFE · 2002 to 2026
$8.8M
PROJECT 4: Interrogating PP2A Signaling in Human CancersP01CA203655 · NCI · DANA-FARBER CANCER INST · PI DECAPRIO, JAMES A. · 2017 to 2021
$8.0M
The DREAM B-Myb-MuvB complex controls sensitivity to DNA replication activators and inhibitorsR35CA232128 · NCI · DANA-FARBER CANCER INST · PI DECAPRIO, JAMES A. · 2019 to 2025
$7.2M
MUC1-C Oncoprotein Evades Immune Destruction in Non-small Cell Lung CancerR01CA166480 · NCI · DANA-FARBER CANCER INST · PI KUFE, DONALD W., WONG, KWOK KIN · 2012 to 2021
$6.3M
MUC1-C is a Target for Reversing Immune Evasion and Resistance to ImmunotherapiesU01CA233084 · NCI · DANA-FARBER CANCER INST · PI KUFE, DONALD W., WONG, KWOK KIN · 2018 to 2022
$4.1M
NCI NIH HHS P01 CA203655NCI NIH HHS R01 CA097098NCI NIH HHS R01 CA166480NCI NIH HHS R35 CA232128NCI NIH HHS U01 CA233084
6 · The paper itself

Abstract

Merkel cell carcinoma (MCC) is an aggressive malignancy with neuroendocrine (NE) features, limited treatment options, and a lack of druggable targets. There is no reported involvement of the MUC1-C oncogenic protein in MCC progression. We show here that MUC1-C is broadly expressed in MCCs and at higher levels in Merkel cell polyomavirus (MCPyV)-positive (MCCP) relative to MCPyV-negative (MCCN) tumors. Our results further demonstrate that MUC1-C is expressed in MCCP, as well as MCCN, cell lines and regulates common sets of signaling pathways related to RNA synthesis, processing, and transport in both subtypes. Mechanistically, MUC1-C (i) interacts with MYCL, which drives MCC progression, (ii) is necessary for expression of the OCT4, SOX2, KLF4, MYC, and NANOG pluripotency factors, and (iii) induces the NEUROD1, BRN2 and ATOH1 NE lineage dictating transcription factors. We show that MUC1-C is also necessary for MCCP and MCCN cell survival by suppressing DNA replication stress, the p53 pathway, and apoptosis. In concert with these results, targeting MUC1-C genetically and pharmacologically inhibits MCC self-renewal capacity and tumorigenicity. These findings demonstrate that MCCP and MCCN cells are addicted to MUC1-C and identify MUC1-C as a potential target for MCC treatment.

Indexed as

Carcinoma, Merkel CellMerkel cell polyomavirusMucin-1Skin NeoplasmsHumansSignal TransductionMUC1 protein, humanMucin-1

Identifiers

PMID35688945
PMCPMC9249628
OpenAlexW4281756494

What Socratic 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 Socratic graph.