Clusterin Modulation in Cancer Progression and Therapeutics

Clusterin, also known as apolipoprotein J, is a multifunctional glycoprotein implicated in cellular stress responses, apoptosis regulation and tumour progression. Its secretory form (sCLU) acts as an extracellular chaperone that shields malignant cells from cytotoxic insults, whereas alternative isoforms such as nuclear clusterin (nCLU) promote cell death in response to genotoxic stress. Dysregulated clusterin expression has been observed across a spectrum of cancers, where it supports chemoresistance by enhancing cancer cell plasticity, stabilising key survival pathways and fostering cancer stem cell phenotypes. Modulation of clusterin levels influences critical signalling cascades—including PI3K/Akt, MAPK and β-catenin axes—thereby affecting cell proliferation, invasion and metastasis. Targeting clusterin through antisense oligonucleotides, small-molecule inhibitors or antibody-mediated neutralisation has emerged as a promising therapeutic strategy. Such approaches aim to suppress sCLU-driven resistance while preserving or enhancing pro-apoptotic isoforms, offering a potential route to overcome treatment failure and improve patient outcomes.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Clusterin Modulation in Cancer Progression and Therapeutics publication trend

The graph below shows the total number of articles in clusterin modulation in cancer progression and therapeutics across all publications each year (not limited to Nature Index journals).

Technical terms

Clusterin (CLU): A stress-responsive glycoprotein with chaperone activity that can either protect cells from apoptosis or, in alternative forms, promote cell death.

Secretory clusterin (sCLU): The extracellular isoform of CLU that inhibits apoptosis and favours tumour cell survival and chemoresistance.

Nuclear clusterin (nCLU): An intracellular isoform produced by alternative splicing that translocates to the nucleus and promotes apoptosis in response to genotoxic stress.

Chemoresistance: The ability of cancer cells to withstand and survive exposure to chemotherapeutic agents, often mediated by adaptive stress responses.

Cancer stem cell (CSC): A subpopulation of tumour cells with self-renewal capacity and enhanced resistance to conventional therapies, contributing to relapse and metastasis.

References

1. Clusterin: a marker and mediator of chemoresistance in colorectal cancer. Cancer and Metastasis Reviews (2024).
2. Therapeutic Potential of Clusterin Inhibition in Human Cancer. Cells (2024).
3. The Ins and Outs of Clusterin: Its Role in Cancer, Eye Diseases and Wound Healing. International Journal of Molecular Sciences (2023).
4. Synthesis and Functional Analyses of Nuclear Clusterin, a Cell Death Protein*. Journal of Biological Chemistry (2003).
5. Clusterin Activates Survival through the Phosphatidylinositol 3-Kinase/Akt Pathway*. Journal of Biological Chemistry (2008).
6. Secretory clusterin promotes hepatocellular carcinoma progression by facilitating cancer stem cell properties via AKT/GSK-3β/β-catenin axis. Journal of Translational Medicine (2020).
7. Delayed Activation of Insulin-like Growth Factor-1 Receptor/Src/MAPK/Egr-1 Signaling Regulates Clusterin Expression, a Pro-survival Factor*. Journal of Biological Chemistry (2005).