Unlocking the Role of OCT4 in Cancer Lineage Plasticity: A Cross-Cancer Perspective with an Emphasis on Prostate Cancer
Prostate cancer (PCa) is a highly heterogeneous disease, with castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC) representing its most aggressive and therapy-resistant forms. Emerging evidence indicates that lineage plasticity—driven by key transcription factors su...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/7/1642 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849407691840028672 |
|---|---|
| author | Mohammad Esfini Farahani Yanquan Zhang Amos Olalekan Akinyemi Fatemeh Seilani Md Rakibul Alam Xiaoqi Liu |
| author_facet | Mohammad Esfini Farahani Yanquan Zhang Amos Olalekan Akinyemi Fatemeh Seilani Md Rakibul Alam Xiaoqi Liu |
| author_sort | Mohammad Esfini Farahani |
| collection | DOAJ |
| description | Prostate cancer (PCa) is a highly heterogeneous disease, with castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC) representing its most aggressive and therapy-resistant forms. Emerging evidence indicates that lineage plasticity—driven by key transcription factors such as Octamer Binding Factor 4 (OCT4)—plays a crucial role in therapeutic resistance and disease progression. OCT4, in coordination with SOX2 and NANOG, acts as a master regulator of stemness and is frequently upregulated in prostate cancer stem cells (PCSCs). This upregulation contributes to tumor initiation, metastasis, and resistance to both androgen deprivation therapy (ADT) and chemotherapy. In this review, we explore the role of OCT4 in mediating lineage plasticity in prostate cancer, with particular emphasis on its involvement in treatment resistance and neuroendocrine differentiation. We also examine therapeutic strategies aimed at targeting OCT4 directly, such as microRNA-mediated suppression, small-molecule inhibitors, and suicide gene therapy, as well as indirect approaches that modulate OCT4 expression via FGFR and NF-κB signaling pathways. While these strategies offer promising avenues, challenges such as adaptive resistance and the intricate signaling networks within PCSCs remain significant hurdles. A deeper understanding of the molecular mechanisms underlying OCT4-driven plasticity may pave the way for novel therapeutic approaches and improved outcomes in advanced prostate cancer. |
| format | Article |
| id | doaj-art-af5b8097ff714bb8871dfa59a96b6530 |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-af5b8097ff714bb8871dfa59a96b65302025-08-20T03:35:58ZengMDPI AGBiomedicines2227-90592025-07-01137164210.3390/biomedicines13071642Unlocking the Role of OCT4 in Cancer Lineage Plasticity: A Cross-Cancer Perspective with an Emphasis on Prostate CancerMohammad Esfini Farahani0Yanquan Zhang1Amos Olalekan Akinyemi2Fatemeh Seilani3Md Rakibul Alam4Xiaoqi Liu5Department of Toxicology and Cancer Biology, Collage of Medicine, University of Kentucky, Lexington, KY 40536, USADepartment of Toxicology and Cancer Biology, Collage of Medicine, University of Kentucky, Lexington, KY 40536, USADepartment of Toxicology and Cancer Biology, Collage of Medicine, University of Kentucky, Lexington, KY 40536, USADepartment of Toxicology and Cancer Biology, Collage of Medicine, University of Kentucky, Lexington, KY 40536, USADepartment of Toxicology and Cancer Biology, Collage of Medicine, University of Kentucky, Lexington, KY 40536, USADepartment of Toxicology and Cancer Biology, Collage of Medicine, University of Kentucky, Lexington, KY 40536, USAProstate cancer (PCa) is a highly heterogeneous disease, with castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC) representing its most aggressive and therapy-resistant forms. Emerging evidence indicates that lineage plasticity—driven by key transcription factors such as Octamer Binding Factor 4 (OCT4)—plays a crucial role in therapeutic resistance and disease progression. OCT4, in coordination with SOX2 and NANOG, acts as a master regulator of stemness and is frequently upregulated in prostate cancer stem cells (PCSCs). This upregulation contributes to tumor initiation, metastasis, and resistance to both androgen deprivation therapy (ADT) and chemotherapy. In this review, we explore the role of OCT4 in mediating lineage plasticity in prostate cancer, with particular emphasis on its involvement in treatment resistance and neuroendocrine differentiation. We also examine therapeutic strategies aimed at targeting OCT4 directly, such as microRNA-mediated suppression, small-molecule inhibitors, and suicide gene therapy, as well as indirect approaches that modulate OCT4 expression via FGFR and NF-κB signaling pathways. While these strategies offer promising avenues, challenges such as adaptive resistance and the intricate signaling networks within PCSCs remain significant hurdles. A deeper understanding of the molecular mechanisms underlying OCT4-driven plasticity may pave the way for novel therapeutic approaches and improved outcomes in advanced prostate cancer.https://www.mdpi.com/2227-9059/13/7/1642octamer-binding transcription factor 4prostate cancer stem cellsandrogen deprivation therapycastration-resistant prostate cancerneuroendocrine prostate cancer |
| spellingShingle | Mohammad Esfini Farahani Yanquan Zhang Amos Olalekan Akinyemi Fatemeh Seilani Md Rakibul Alam Xiaoqi Liu Unlocking the Role of OCT4 in Cancer Lineage Plasticity: A Cross-Cancer Perspective with an Emphasis on Prostate Cancer Biomedicines octamer-binding transcription factor 4 prostate cancer stem cells androgen deprivation therapy castration-resistant prostate cancer neuroendocrine prostate cancer |
| title | Unlocking the Role of OCT4 in Cancer Lineage Plasticity: A Cross-Cancer Perspective with an Emphasis on Prostate Cancer |
| title_full | Unlocking the Role of OCT4 in Cancer Lineage Plasticity: A Cross-Cancer Perspective with an Emphasis on Prostate Cancer |
| title_fullStr | Unlocking the Role of OCT4 in Cancer Lineage Plasticity: A Cross-Cancer Perspective with an Emphasis on Prostate Cancer |
| title_full_unstemmed | Unlocking the Role of OCT4 in Cancer Lineage Plasticity: A Cross-Cancer Perspective with an Emphasis on Prostate Cancer |
| title_short | Unlocking the Role of OCT4 in Cancer Lineage Plasticity: A Cross-Cancer Perspective with an Emphasis on Prostate Cancer |
| title_sort | unlocking the role of oct4 in cancer lineage plasticity a cross cancer perspective with an emphasis on prostate cancer |
| topic | octamer-binding transcription factor 4 prostate cancer stem cells androgen deprivation therapy castration-resistant prostate cancer neuroendocrine prostate cancer |
| url | https://www.mdpi.com/2227-9059/13/7/1642 |
| work_keys_str_mv | AT mohammadesfinifarahani unlockingtheroleofoct4incancerlineageplasticityacrosscancerperspectivewithanemphasisonprostatecancer AT yanquanzhang unlockingtheroleofoct4incancerlineageplasticityacrosscancerperspectivewithanemphasisonprostatecancer AT amosolalekanakinyemi unlockingtheroleofoct4incancerlineageplasticityacrosscancerperspectivewithanemphasisonprostatecancer AT fatemehseilani unlockingtheroleofoct4incancerlineageplasticityacrosscancerperspectivewithanemphasisonprostatecancer AT mdrakibulalam unlockingtheroleofoct4incancerlineageplasticityacrosscancerperspectivewithanemphasisonprostatecancer AT xiaoqiliu unlockingtheroleofoct4incancerlineageplasticityacrosscancerperspectivewithanemphasisonprostatecancer |