Researchers Uncover New Role for Transcription Factor in Castration-Resistant Prostate Cancer
A new study from the Department of Cancer Biology at Loyola University Chicago sheds light on a significant shift in the function of NKX3.1, a protein previously regarded as a tumor suppressor in prostate cancer. Published in MDPI Cancers, the research reveals that NKX3.1 may promote tumor growth in advanced forms of the disease, offering new insights into therapy resistance and disease progression.
NKX3.1 is a homeobox transcription factor critical for normal prostate development and function. In early-stage prostate cancer, it has long been characterized as a tumor suppressor. However, this new study “The Homeobox Transcription Factor NKX3.1 Displays an Oncogenic Role in Castration-Resistant Prostate Cancer Cells” demonstrates that NKX3.1 adopts a tumor-promoting role in castration-resistant prostate cancer (CRPC), a lethal and treatment-resistant stage of the disease.
What is Castration-Resistant Prostate Cancer?
Castration-resistant prostate cancer (CRPC) refers to a form of prostate cancer that continues to grow despite therapies that target the androgen signaling axis. Once castration-resistance arises, these tumors are no longer responsive to standard-of-care therapies and represent a major clinical challenge for men with disease.
The research team of Audris Budreika, John T. Phoenix, Raymond J. Kostlan, Carleen D. Deegan, Marina G. Ferrari, Kristen S. Young, Sean W. Fanning, and Steven Kregel investigated how NKX3.1 interacts with the AR, the central driver of prostate cancer progression. Although AR-targeted therapies remain the cornerstone of treatment, most patients with advanced disease eventually develop resistance. NKX3.1, which is regulated by AR, may contribute to this process.
What is a Homeobox Transcription Factor?
A homeobox transcription factor is a type of protein that binds to specific DNA sequences to control the activity of genes essentially turning them "on" or "off." These proteins are defined by the presence of a homeobox, a short stretch of DNA that codes for a homeodomain, the part of the protein that attaches to DNA.
Homeobox transcription factors play crucial roles in:
- Early development – helping guide the formation of body structures and organs.
- Cell identity and differentiation – determining how cells specialize and function.
- Tissue maintenance – regulating gene expression in mature tissues, like the prostate.
In the case of NKX3.1, it is a prostate-specific homeobox transcription factor that’s normally involved in maintaining healthy prostate tissue. However, as this new study shows, its role may shift in advanced cancer, helping tumors survive and grow under conditions that typically suppress prostate cell growth.
What Were the Findings?
The study found that NKX3.1 expression is often elevated in CRPC due to continued AR signaling, even in androgen-deprived or AR-inhibited conditions. Knockdown of NKX3.1 led to reduced CRPC cell survival, while NKX3.1 overexpression allowed CRPC cells to grow more effectively and resist AR-targeted therapy.
These findings indicate that NKX3.1 functions as a critical AR cofactor and may promote the expression of select AR target genes involved in cancer cell proliferation and survival. The results support a model in which NKX3.1, like AR, plays a context-dependent role suppressing tumors in early-stage disease while promoting growth in advanced cancer.
This work contributes to a deeper understanding of transcriptional regulation in CRPC and highlights NKX3.1 as a potential target for future therapeutic strategies, particularly in cases where standard AR-directed treatments are no longer effective.
The study was conducted at Loyola’s Cardinal Bernardin Cancer Center and aligns with the university’s mission to advance translational cancer research.
Be a Force for Discovery in Biomedical Science
At Loyola University Chicago, our Graduate Biomedical Sciences programs don’t just teach science, they shape scientists ready to change the world. Whether you're decoding the mysteries of cell biology or developing tomorrow’s therapies, you’ll join a dynamic community driven by curiosity, collaboration, and impact.
Explore how you can be part of this bold journey by following the link learn more, and take the first step by applying today.
A new study from the Department of Cancer Biology at Loyola University Chicago sheds light on a significant shift in the function of NKX3.1, a protein previously regarded as a tumor suppressor in prostate cancer. Published in MDPI Cancers, the research reveals that NKX3.1 may promote tumor growth in advanced forms of the disease, offering new insights into therapy resistance and disease progression.
NKX3.1 is a homeobox transcription factor critical for normal prostate development and function. In early-stage prostate cancer, it has long been characterized as a tumor suppressor. However, this new study “The Homeobox Transcription Factor NKX3.1 Displays an Oncogenic Role in Castration-Resistant Prostate Cancer Cells” demonstrates that NKX3.1 adopts a tumor-promoting role in castration-resistant prostate cancer (CRPC), a lethal and treatment-resistant stage of the disease.
What is Castration-Resistant Prostate Cancer?
Castration-resistant prostate cancer (CRPC) refers to a form of prostate cancer that continues to grow despite therapies that target the androgen signaling axis. Once castration-resistance arises, these tumors are no longer responsive to standard-of-care therapies and represent a major clinical challenge for men with disease.
The research team of Audris Budreika, John T. Phoenix, Raymond J. Kostlan, Carleen D. Deegan, Marina G. Ferrari, Kristen S. Young, Sean W. Fanning, and Steven Kregel investigated how NKX3.1 interacts with the AR, the central driver of prostate cancer progression. Although AR-targeted therapies remain the cornerstone of treatment, most patients with advanced disease eventually develop resistance. NKX3.1, which is regulated by AR, may contribute to this process.
What is a Homeobox Transcription Factor?
A homeobox transcription factor is a type of protein that binds to specific DNA sequences to control the activity of genes essentially turning them "on" or "off." These proteins are defined by the presence of a homeobox, a short stretch of DNA that codes for a homeodomain, the part of the protein that attaches to DNA.
Homeobox transcription factors play crucial roles in:
- Early development – helping guide the formation of body structures and organs.
- Cell identity and differentiation – determining how cells specialize and function.
- Tissue maintenance – regulating gene expression in mature tissues, like the prostate.
In the case of NKX3.1, it is a prostate-specific homeobox transcription factor that’s normally involved in maintaining healthy prostate tissue. However, as this new study shows, its role may shift in advanced cancer, helping tumors survive and grow under conditions that typically suppress prostate cell growth.
What Were the Findings?
The study found that NKX3.1 expression is often elevated in CRPC due to continued AR signaling, even in androgen-deprived or AR-inhibited conditions. Knockdown of NKX3.1 led to reduced CRPC cell survival, while NKX3.1 overexpression allowed CRPC cells to grow more effectively and resist AR-targeted therapy.
These findings indicate that NKX3.1 functions as a critical AR cofactor and may promote the expression of select AR target genes involved in cancer cell proliferation and survival. The results support a model in which NKX3.1, like AR, plays a context-dependent role suppressing tumors in early-stage disease while promoting growth in advanced cancer.
This work contributes to a deeper understanding of transcriptional regulation in CRPC and highlights NKX3.1 as a potential target for future therapeutic strategies, particularly in cases where standard AR-directed treatments are no longer effective.
The study was conducted at Loyola’s Cardinal Bernardin Cancer Center and aligns with the university’s mission to advance translational cancer research.
Be a Force for Discovery in Biomedical Science
At Loyola University Chicago, our Graduate Biomedical Sciences programs don’t just teach science, they shape scientists ready to change the world. Whether you're decoding the mysteries of cell biology or developing tomorrow’s therapies, you’ll join a dynamic community driven by curiosity, collaboration, and impact.
Explore how you can be part of this bold journey by following the link learn more, and take the first step by applying today.