Combination of Radiation Treatment and PLK4-Inhibitor, CFI-400945, Leads to Upregulation of ICAM-1, STAT3 Activation, and Cellular Senescence in TNBC
Abstract
Background Triple-negative breast cancer (TNBC) is one of the most aggressive and highly metastatic subtypes of breast cancer. It lacks canonical biomarkers and is often resistant to treatments, including radiotherapy (RT). This mandates the development of better treatments through identifying novel therapeutic targets and biomarkers in TNBC to improve patient stratification for treatment and facilitate novel drug development. We have previously shown that anticancer effects of RT are synergized by the inhibition of polo-like kinase 4 (PLK4) by CFI-400945. Objectives, Design and Methods In the present study, we aimed to obtain mechanistic insights of the anticancer effects of RT in combination with CFI-400945 using bulk RNA-sequencing in MDA-MB-231 TNBC cells treated with single agents and their combination. Results Differential gene expression (DEG) and pathway enrichment analyses of the bulk transcriptomics data have identified perturbations in immune and senescence related genes and pathways in TNBC cells treated with RT alone or in combination with CFI-400945. Validation of the identified DEGs showed significant upregulation of ICAM - 1 (Intercellular Adhesion Molecule-1) both at transcript and protein levels following combination treatment compared to untreated control cells. This was accompanied by activation of STAT3 protein and increased cellular senescence determined by β-galactosidase assay in combination treatment compared to untreated control. Conclusion Overall, our data suggest that ICAM-1 and STAT3 signaling axis may play an important role in TNBC cell response to RT and PLK4 inhibition.
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BibTeX
@article{kannampuzha2026combination,
title = {{Combination of Radiation Treatment and PLK4-Inhibitor, CFI-400945, Leads to Upregulation of ICAM-1, STAT3 Activation, and Cellular Senescence in TNBC}},
author = {Isabel Kannampuzha and Vasudeva Bhat and Sugitha Janarthanan and Harjot K. Athwal and Kaitlyn E. Wade and Pingzhao Hu and Alison L. Allan and Armen Parsyan},
journal = {Breast Cancer: Basic and Clinical Research},
year = {2026},
month = oct,
doi = {10.1177/11782234261496004},
url = {https://doi.org/10.1177/11782234261496004},
note = {CC BY},
}
RIS
TY - JOUR
TI - Combination of Radiation Treatment and PLK4-Inhibitor, CFI-400945, Leads to Upregulation of ICAM-1, STAT3 Activation, and Cellular Senescence in TNBC
AU - Isabel Kannampuzha
AU - Vasudeva Bhat
AU - Sugitha Janarthanan
AU - Harjot K. Athwal
AU - Kaitlyn E. Wade
AU - Pingzhao Hu
AU - Alison L. Allan
AU - Armen Parsyan
PY - 2026
DA - 2026/10/24
JO - Breast Cancer: Basic and Clinical Research
DO - 10.1177/11782234261496004
UR - https://doi.org/10.1177/11782234261496004
AB - Background Triple-negative breast cancer (TNBC) is one of the most aggressive and highly metastatic subtypes of breast cancer. It lacks canonical biomarkers and is often resistant to treatments, including radiotherapy (RT). This mandates the development of better treatments through identifying novel therapeutic targets and biomarkers in TNBC to improve patient stratification for treatment and facilitate novel drug development. We have previously shown that anticancer effects of RT are synergized by the inhibition of polo-like kinase 4 (PLK4) by CFI-400945. Objectives, Design and Methods In the present study, we aimed to obtain mechanistic insights of the anticancer effects of RT in combination with CFI-400945 using bulk RNA-sequencing in MDA-MB-231 TNBC cells treated with single agents and their combination. Results Differential gene expression (DEG) and pathway enrichment analyses of the bulk transcriptomics data have identified perturbations in immune and senescence related genes and pathways in TNBC cells treated with RT alone or in combination with CFI-400945. Validation of the identified DEGs showed significant upregulation of ICAM - 1 (Intercellular Adhesion Molecule-1) both at transcript and protein levels following combination treatment compared to untreated control cells. This was accompanied by activation of STAT3 protein and increased cellular senescence determined by β-galactosidase assay in combination treatment compared to untreated control. Conclusion Overall, our data suggest that ICAM-1 and STAT3 signaling axis may play an important role in TNBC cell response to RT and PLK4 inhibition.
SN - 1178-2234
ER -