Close

Refine your search

Transcription factor crosstalk in cancers - Paakinaho lab´s Profile image

Transcription factor crosstalk in cancers - Paakinaho lab

Research group
01.01.2022 -
Institute of Biomedicine, School of Medicine, Faculty of Health Sciences
Information People Publications

Leaders

Our research aims to decipher the key transcriptional mechanism mediated by steroid receptors and pioneer factors in health and disease. Our specific interests are with transcription factor crosstalk in prostate cancer; how steroid receptors and pioneer factors alter each other’s activity impacting cancer initiation, development, and drug resistance. Special emphasis is placed from the steroid receptors on the glucocorticoid receptor (GR) and androgen receptor (AR), and from the pioneer factors on the forkhead box A1 (FOXA1) and activator protein 1 (AP-1). In our research we utilize genome-wide deep sequencing, chromatin proteomic, single-cell genomic, and CRISPR genome editing techniques. We aim to discover new therapeutic targets and forms of treatment to overcome advanced and drug therapy resistant cancers. Our findings may also be applicable to research in other disease areas, including metabolic disorders.

Research group:
Ville Paakinaho
Academy Research Fellow, PhD, Title of a Docent (molecular endocrinology)

Project researcher, PhD Niina Aaltonen
Doctoral researcher, MSc Laura Helminen
Doctoral researcher, MSc Johannes Hiltunen
Doctoral researcher, MSc Jasmin Huttunen
Research trainee, MSc Mitali Mishra
Research trainee, BSc Heini Sohlberg

Research projects:
(i) Transcription factor crosstalk mechanism in benign versus malignant prostate cancer cells.
(ii) Steroid receptor-mediated drug therapy resistance in prostate cancer cells.
(iii) Coregulators in transcription factor crosstalk and their impact in therapy naïve and drug therapy resistant prostate cancer cells.

Research results:
Our recent research has demonstrated that FOXA1 plays a crucial role in GR-mediated drug resistance and that transcription factor crosstalk can be leveraged to counteract its harmful effects in prostate cancer (Helminen et al., 2024, Nucleic Acids Res; Huttunen et al., 2024, Cell Mol Life Sci). We have also discovered that GR restricts the progress of prostate cancer in the presence of AR, while it mediates the survival of the cancer in the absence of AR (Hiltunen et al., 2025, Genome Res).

 

News

  • Preprint publication: bioRxiv

    p63-GATA2 molecular switch mediates the tumor suppressor to oncogene transition of glucocorticoid receptor in the prostate

  • The glucocorticoid receptor is a double-edged sword in prostate cancer

    A recent study from the Institute of Biomedicine at the University of Eastern Finland shows that the glucocorticoid receptor can both promote and…

  • Research publication: Genome Res

    Androgen receptor-mediated assisted loading of the glucocorticoid receptor modulates transcriptional responses in prostate cancer cells

Our research goals and results

For background information, see the following review articles related to our research topics:

2018 Swinstead, Paakinaho, Hager: Chromatin reprogramming in breast cancer

2021 Paakinaho, Palvimo: Genome-wide crosstalk between steroid receptors in breast and prostate cancers

2024 Hiltunen, Helminen, Paakinaho: Glucocorticoid receptor action in prostate cancer: the role of transcription factor crosstalk

Research goals

Our research aims to decipher several aspects in transcription factor (TF) crosstalk:

(i) What kind of crosstalk mechanism occur between steroid receptors and pioneer factors in benign versus malignant prostate cancer cells.

(ii) How and through what mechanism does GR replace AR signaling in antiandrogen-resistant prostate cancer cells.

(iii) To what degree does coregulators influence TF crosstalk in therapy naïve and antiandrogen-resistant prostate cancer cells.

(iv) Which prostate cancer TF crosstalk mechanisms can be observed in other cancer cell types.

We anticipate that our findings will open new therapeutic avenues for targeting coordinated TF activity in the prostate. Specifically, dual targeting of steroid receptors, pioneer factors, and their coregulators may offer a strategy to overcome drug resistance commonly observed with single-agent therapies. Additionally, modulating GR activity through alternative signaling pathways in antiandrogen-resistant prostate cancer could preserve the systemic benefits of glucocorticoids while minimizing their oncogenic potential. Importantly, we expect that the mechanistic insights gained from this study can be extended to other cancer types, and potentially to non-cancerous diseases, such as metabolic disorders, where TFs play critical regulatory roles.

Research results

For Research aim (i), we have published our results in Genome Res -journal:

Androgen receptor-mediated assisted loading of the glucocorticoid receptor modulates transcriptional responses in prostate cancer cells

The datasets associated with the publication can be accessed here: GSE266217

 

For Research aim (ii), we have published our results in Nucleic Acids Res -journal:

Chromatin accessibility and pioneer factor FOXA1 restrict glucocorticoid receptor action in prostate cancer

The datasets associated with the publication can be accessed here: GSE214757

 

For Research aim (iii), we have published our results in Cell Mol Life Sci -journal:

EP300/CREBBP acetyltransferase inhibition limits steroid receptor and FOXA1 signaling in prostate cancer cells

The datasets associated with the publication can be accessed here: GSE245969

Lab news

2025-08: The second bioRxiv preprint for Research project (i) is published.

2025-06: Research project (i) results are published in Genome Res -journal.

2024-11: bioRxiv preprint for Research project (i) is published.

2024-09: Johannes and Laura presented their results at EMBO Nuclear Receptor meeting.

2024-07: Review article from our research field is published in Front Endocrinol -journal.

2024-04: Research project (iii) results are published in Cell Mol Life Sci -journal.

2023-11: Research project (ii) results are published in Nucleic Acids Res -journal. Laura presented her research results at EMBL Cancer genomics meeting.

2023-10

Team bouldering
Team bouldering

2023-08: Johannes presented his research results at FEBS Epigenomics, Nuclear Receptors and Diseases meeting.

2023-06: Ville presented the results from the research group at ENDO 2023 meeting.

2023-03: bioRxiv preprint for Research project (ii) is published.

Keywords

cancer research chromatin genomics molecular biology molecular endocrinology

Leaders

Post-doctoral Researchers

Doctoral Researchers

Supporting Staff

Publications

4 items