Omics · study · 2026
Upregulation of E-cadherin Promotes Spheroid Formation in Crizotinib-Resistant ALK-rearranged Lung Cancer
Listed in NCBI GEO
The anaplastic lymphoma kinase (ALK) gene fusion functions as a potent oncogene in lung cancer.
Description
The development of ALK tyrosine kinase inhibitors has improved patient outcomes. However, cancer progression commonly occurs even after treatment.
Chemoresistance arises mostly by the acquisition of gatekeeper mutations in ALK as well as by off-target bypass mechanisms arising during chemotherapy. To investigate these bypass mechanisms, we studied crizotinib resistance in ALK-rearranged lung cancer by using 2D and 3D cell line models and longitudinal human biopsy samples. We found that crizotinib-resistant H2228 cells exhibited increased tumor cell clustering and spheroid formation, with elevated E-cadherin levels.
Read the rest (2 more)
Notably, depletion of E-cadherin profoundly disrupted spheroid formation and restored drug sensitivity. Transcriptomic profiling revealed the upregulation of tissue morphology-related genes; in particular, EpCAM was highly expressed in the protrusive regions of spheroids. Remarkably, longitudinal biopsy analysis also demonstrated enhanced expression of E-cadherin and EpCAM in patients with ALK-rearranged lung cancer during chemotherapy.
We propose that off-target resistance is mediated by the upregulation of morphogenic genes, which drive cell clustering and spheroid formation during tumor evolution. To overcome chemoresistance, it is crucial to monitor tumor evolution during treatment. Tracking the collective migration of cells may present a novel therapeutic target.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE284nnn/GSE284648 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE284648 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1199995 ncbi.nlm.nih.gov/bioproject/PRJNA1199995 ↗
project · from NCBI GEO
- PubMed 41679471 pubmed.ncbi.nlm.nih.gov/41679471 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75% · Longitudinal study 65%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE284648 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[method].local:method:longitudinal-study | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |