Journal: Molecules and Cells

Article Title: E-cadherin–driven adherens junction reinforcement promotes spheroid-mediated invasion and progression in ALK–rearranged lung cancer chemoresistance

doi: 10.1016/j.mocell.2026.100329

Figure Lengend Snippet: E-cadherin modulates crizotinib sensitivity in ALK–rearranged H2228 cells. (A) Cell survival of H2228, H2228-CR1, and H2228-CR2 cells following E-cadherin knockdown using siE-cad compared with control siRNA (siCon). (B) Half-maximal inhibitory concentration (IC 50 ) values for crizotinib in H2228 and H2228-CR2 cells after transfection with siCon or siE-cad. (C) Cell survival of parental H2228 cells following expression of FLAG-tagged E-cadherin (FLAG-E-cad) compared with empty vector (vec). (D) IC 50 values for crizotinib in parental H2228 cells expressing Vec or FLAG-E-cad.

Article Snippet: The following siRNA oligonucleotides were used: control siRNA-A (sc-37007), E-cadherin siRNA (sc-35242), and EpCAM siRNA (sc-43032), all purchased from Santa Cruz Biotechnology.

Techniques: Knockdown, Control, Concentration Assay, Transfection, Expressing, Plasmid Preparation

Journal: Molecules and Cells

Article Title: E-cadherin–driven adherens junction reinforcement promotes spheroid-mediated invasion and progression in ALK–rearranged lung cancer chemoresistance

doi: 10.1016/j.mocell.2026.100329

Figure Lengend Snippet: RNA sequencing reveals the upregulation of tissue morphogenic transcripts in crizotinib–resistant H2228 cells. (A) Volcano plot showing significantly differentially expressed genes (DEGs) between parental H2228 and crizotinib–resistant H2228-CR1 and H2228-CR2 cells. Red and blue dots indicate upregulated and downregulated genes, respectively; arrow indicates CDH1 . (B) Functional enrichment analysis of commonly upregulated DEGs in H2228-CR1 and H2228-CR2 cells using Metascape. (C) Heatmap showing the mean log2 fold change of selected DEGs in H2228-CR1 and H2228-CR2 cells. (D) Correlation analysis between CDH1 and selected epithelial junction–related genes ( EpCAM, CLDNs, and GJB3 ) in lung adenocarcinoma (LUAD) patients using GEPIA2 base. (E) Quantitative real–time PCR analysis of EpCAM mRNA expression in parental H2228, H2228-CR1, and H2228-CR2 cells. (F) Western blot analysis of EpCAM protein levels in parental H2228, H2228-CR1, and H2228-CR2 cells. β-actin was used as a loading control.

Article Snippet: The following siRNA oligonucleotides were used: control siRNA-A (sc-37007), E-cadherin siRNA (sc-35242), and EpCAM siRNA (sc-43032), all purchased from Santa Cruz Biotechnology.

Techniques: RNA Sequencing, Functional Assay, Real-time Polymerase Chain Reaction, Expressing, Western Blot, Control

Journal: Molecules and Cells

Article Title: E-cadherin–driven adherens junction reinforcement promotes spheroid-mediated invasion and progression in ALK–rearranged lung cancer chemoresistance

doi: 10.1016/j.mocell.2026.100329

Figure Lengend Snippet: EpCAM regulates migration and invasion in crizotinib-resistant spheroids. (A) Immunofluorescence analysis of EpCAM (green) and E-cadherin (red) localization in 3D Matrigel-cultured spheroids of parental H2228 and H2228-CR2 cells. (B) Fluorescence intensity mapping along the white dashed line shown in (A). Peri. region, peripheral protrusive region; AJ, adherens junction. (C) Bright-field images of collagen I-embedded spheroids derived from parental H2228 and H2228-CR2 cells following transfected with sicontrol (sicon) or siEpCAM. (D) Transwell invasion assays using spheroids from parental H2228 and H2228-CR2 cells transfected with sicon or siEpCAM.

Article Snippet: The following siRNA oligonucleotides were used: control siRNA-A (sc-37007), E-cadherin siRNA (sc-35242), and EpCAM siRNA (sc-43032), all purchased from Santa Cruz Biotechnology.

Techniques: Migration, Immunofluorescence, Cell Culture, Fluorescence, Derivative Assay, Transfection

Journal: Molecules and Cells

Article Title: E-cadherin–driven adherens junction reinforcement promotes spheroid-mediated invasion and progression in ALK–rearranged lung cancer chemoresistance

doi: 10.1016/j.mocell.2026.100329

Figure Lengend Snippet: Immunohistochemistry of E-cadherin and EpCAM on longitudinal biopsy samples of patients with ALK–rearranged pulmonary adenocarcinoma (N = 23). (A) Workflow of pathological study. (B) Representative images of E-cadherin expression (×200). (C) Significantly higher E-cadherin expression was observed in the second biopsy specimen than in the first biopsy specimen. (D) Representative images of EpCAM expression (×20). (E) EpCAM expression increased significantly in the second biopsy specimen compared to that in the first biopsy specimen.

Article Snippet: The following siRNA oligonucleotides were used: control siRNA-A (sc-37007), E-cadherin siRNA (sc-35242), and EpCAM siRNA (sc-43032), all purchased from Santa Cruz Biotechnology.

Techniques: Immunohistochemistry, Expressing

Journal: Molecules and Cells

Article Title: E-cadherin–driven adherens junction reinforcement promotes spheroid-mediated invasion and progression in ALK–rearranged lung cancer chemoresistance

doi: 10.1016/j.mocell.2026.100329

Figure Lengend Snippet: Schematic diagram illustrating the role of E-cadherin and EpCAM in promoting spheroid and invasion in crizotinib–resistant ALK–rearranged lung cancer. In the upper panel, crizotinib–resistant H2228 lung cancer cells with EML4-ALK fusion exhibit enhanced morphogenic features, forming compact spheroids with elevated E-cadherin and EpCAM expression. RNA-seq analysis reveals enrichment of morphogenesis–related gene signatures. Reinforced adherens junctions (via E-cadherin) and the accumulation of EpCAM–marked protrusive cells contribute to invasion. In the lower panel, longitudinal biopsy samples from ALK–rearranged lung cancer patients show increased E-cadherin and EpCAM expression at the time of cancer progression, supporting the clinical relevance of adhesion-driven survival and structural remodeling in tumor progression.

Article Snippet: The following siRNA oligonucleotides were used: control siRNA-A (sc-37007), E-cadherin siRNA (sc-35242), and EpCAM siRNA (sc-43032), all purchased from Santa Cruz Biotechnology.

Techniques: Expressing, RNA Sequencing