Evidence map›Paper›PMID 35173310›Full record

ArticleOncogene2022

EMT-mediated regulation of CXCL1/5 for resistance to anti-EGFR therapy in colorectal cancer.

Ye-Lim Park, Hwang-Phill Kim, Chan-Young Ock, Dong-Wook Min, Jun Kyu Kang, Yoo Joo Lim, Sang-Hyun Song, Sae-Won Han, Tae-You Kim

Abstract read
PubMed Publisher
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 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.0field-weighted citation impact, top 12% 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

20 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Nutrients Lowering Obesity-Linked Chemokines Blamable for Metastasis.International journal of molecular sciences · 2025
    Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Bioinformatic Analysis of the CXCR2 Ligands in Cancer Processes.International journal of molecular sciences · 2023
    Article
  17. Review
  18. Review
  19. Article
  20. 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

9 authors at 3 institutions in 3 countries.

Ye-Lim Park *Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea. yelim_park@snu.ac.kr.
Hwang-Phill Kim *Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.ORCID http://orcid.org/0000-0002-3043-9984
Chan-Young OckDepartment of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Dong-Wook MinCancer Research Institute, Seoul National University, Seoul, Korea.
Jun Kyu KangDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.
Yoo Joo LimDepartment of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Sang-Hyun SongCancer Research Institute, Seoul National University, Seoul, Korea.
Sae-Won HanCancer Research Institute, Seoul National University, Seoul, Korea.
Tae-You KimDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea. kimty@snu.ac.kr.ORCID http://orcid.org/0000-0002-4336-8222
Seoul National University · KRSeoul National University Hospital · KRSeoul National University of Science and Technology · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The emergence of RAS/RAF mutant clone is the main feature of EGFR inhibitor resistance in KRAS wild-type colon cancer. However, its molecular mechanism is thought to be multifactorial, mainly due to cellular heterogeneity. In order to better understand the resistance mechanism in a single clone level, we successfully isolated nine cells with cetuximab-resistant (CR) clonality from in vitro system. All CR cells harbored either KRAS or BRAF mutations. Characteristically, these cells showed a higher EMT (Epithelial to mesenchymal transition) signature, showing increased EMT markers such as SNAI2. Moreover, the expression level of CXCL1/5, a secreted protein, was significantly higher in CR cells compared to the parental cells. In these CR cells, CXCL1/5 expression was coordinately regulated by SNAI2/NFKB and transactivated EGFR through CXCR/MMPI/EGF axis via autocrine singling. We also observed that combined cetuximab/MEK inhibitor not only showed growth inhibition but also reduced the secreted amounts of CXCL1/5. We further found that serum CXCL1/5 level was positively correlated with the presence of RAS/RAF mutation in colon cancer patients during cetuximab therapy, suggesting its role as a biomarker. These data indicated that the application of serum CXCL1/5 could be a potential serologic biomarker for predicting resistance to EGFR therapy in colorectal cancer.

Indexed as

Colorectal NeoplasmsEpithelial-Mesenchymal TransitionCetuximabChemokine CXCL1Chemokine CXCL5Drug Resistance, NeoplasmErbB ReceptorsHumansMutationProtein Kinase InhibitorsProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)CetuximabChemokine CXCL1Chemokine CXCL5CXCL1 protein, humanCXCL5 protein, humanErbB ReceptorsProtein Kinase InhibitorsProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)

Identifiers

PMID35173310
OpenAlexW4212788864

What OpenQuestion holds

Textmetadata
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.