Related Experiment Video
Updated: Oct 4, 2025
Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres
Published on: July 22, 2020
Chemogenomic and bioinformatic profiling of ERdj paralogs underpins their unique roles in cancer
Laura E Knighton1, Nitika1, Tasaduq H Wani1
1Department of Biological Sciences, University of North Carolina Charlotte, Charlotte, NC, 28223, USA.
Abstract:
The ER-resident Hsp70 paralog BiP is important in cellular homeostasis as well as in cancer cell progression. Although several BiP inhibitors have been developed, they have not succeeded in clinical trials due to toxicity issues. ER-resident co-chaperones (ERdjs) tailor the activity and specificity of BiP. Here, we report multiple-cancer analyses of BiP and ERdj genomic alterations including mRNA expression from cancer patients using available data from The Cancer Genome Atlas (TCGA). We examine the individual roles of BiP co-chaperones ERdj1-8 in mediating anticancer drug resistance through chemogenomic screening of ERdj1-8 CRISPR KO cells. In keeping with the idea that ERdjs regulate distinct facets of proteostasis, we find that each ERdj KO displays a unique signature of drug resistance. Taken together, our results demonstrate a novel way to understand functional specificity of ERdjs, suggesting a future personalized medicine approach, whereby ERdj mutation status is assessed to design an effective anticancer treatment plan.
Insights
This study reveals how endoplasmic reticulum co-chaperones (ERdjs) influence cancer drug resistance. Understanding ERdj roles offers a new strategy for personalized cancer medicine.
Area of Science:
- Cellular Biology
- Cancer Research
- Molecular Medicine
Background:
- The Hsp70 paralog BiP is crucial for cellular homeostasis and cancer progression.
- Existing BiP inhibitors face clinical challenges due to toxicity.
- Endoplasmic reticulum co-chaperones (ERdjs) modulate BiP activity and specificity.
Purpose of the Study:
- To analyze genomic alterations and mRNA expression of BiP and ERdjs in cancer patients using TCGA data.
- To investigate the individual roles of ERdj1-8 in anticancer drug resistance.
- To explore ERdjs as potential targets for personalized cancer therapy.
Main Methods:
- Analysis of The Cancer Genome Atlas (TCGA) data for BiP and ERdj genomic alterations and mRNA expression.
- Chemogenomic screening of ERdj1-8 CRISPR knockout (KO) cell lines.
- Assessment of drug resistance profiles in ERdj KO cells.
Main Results:
- Genomic alterations and differential mRNA expression of BiP and ERdjs were identified across multiple cancer types.
- Each ERdj knockout cell line exhibited a unique drug resistance profile.
- ERdjs play distinct roles in mediating resistance to various anticancer drugs.
Conclusions:
- ERdjs exhibit functional specificity in regulating proteostasis and drug resistance.
- ERdj mutation status can inform personalized anticancer treatment strategies.
- Targeting ERdjs presents a novel avenue for developing effective cancer therapies.
Related Concept Videos
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:38Mitogens and the Cell Cycle
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...