CLU, also known as clusterin and apolipoprotein J (apoJ), is a highly evolutionary conserved glycoprotein. It functions as a molecular chaperone, involved in a broad range of physiological and pathophysiological processes, exerting a cytoprotective role [2]. It participates in regulating programmed cell death, metastasis, invasion, proliferation, and cell growth via diverse signaling pathways in cancer [3]. In the context of Alzheimer's disease, it is related to processes like amyloid-beta handling and neuroinflammation [4].

In oral cancer cells, CLU localizes to mitochondria and acts as an adaptor protein to induce mitophagy, controlling mitochondrial damage. It coordinates with BAX and LC3 to recruit autophagic machinery around damaged mitochondria in response to cisplatin treatment [1]. In oral cancer stem cells, cisplatin treatment activates higher mitophagy through regulating CLU levels. CLU promotes mitophagic degradation of MSX2, maintaining SOX2-mediated stemness [5].

In conclusion, CLU plays essential roles in cancer cell survival by regulating mitophagy and mitochondrial biogenesis in oral cancer [1]. It also has a significant impact on the stemness of oral cancer stem cells through mitophagic regulation [5]. These findings from in-vitro studies related to cancer cells contribute to understanding the role of CLU in cancer, potentially guiding the development of targeted cancer therapies.

References:

1. Praharaj, Prakash P, Patra, Srimanta, Singh, Amruta, Chae, Han J, Bhutia, Sujit K. 2024. CLU (clusterin) and PPARGC1A/PGC1α coordinately control mitophagy and mitochondrial biogenesis for oral cancer cell survival. In Autophagy, 20, 1359-1382. doi:10.1080/15548627.2024.2309904. https://pubmed.ncbi.nlm.nih.gov/38447939/

2. Rohne, Philipp, Prochnow, Hans, Koch-Brandt, Claudia. . The CLU-files: disentanglement of a mystery. In Biomolecular concepts, 7, 1-15. doi:10.1515/bmc-2015-0026. https://pubmed.ncbi.nlm.nih.gov/26673020/

3. Zhang, Yefei, Lv, Xiang, Chen, Liming, Liu, Yan. 2022. The role and function of CLU in cancer biology and therapy. In Clinical and experimental medicine, 23, 1375-1391. doi:10.1007/s10238-022-00885-2. https://pubmed.ncbi.nlm.nih.gov/36098834/

4. Uddin, Md Sahab, Kabir, Md Tanvir, Begum, Mst Marium, Behl, Tapan, Ashraf, Ghulam Md. 2020. Exploring the Role of CLU in the Pathogenesis of Alzheimer's Disease. In Neurotoxicity research, 39, 2108-2119. doi:10.1007/s12640-020-00271-4. https://pubmed.ncbi.nlm.nih.gov/32820456/

5. Praharaj, Prakash P, Patra, Srimanta, Mishra, Soumya R, Patil, Shankargouda, Bhutia, Sujit K. 2023. CLU (clusterin) promotes mitophagic degradation of MSX2 through an AKT-DNM1L/Drp1 axis to maintain SOX2-mediated stemness in oral cancer stem cells. In Autophagy, 19, 2196-2216. doi:10.1080/15548627.2023.2178876. https://pubmed.ncbi.nlm.nih.gov/36779631/