Updates

We are delighted to announce the release of our latest publication by Jenny Pessa, titled “HSF2 drives breast cancer progression by acting as a stage-specific switch between proliferation and invasion”, in collaboration with Emilia Peuhu, Adjucant Professor at the University of Turku.

Breast cancer is characterized by dynamic phenotypic transitions that enable abnormal cell proliferation and invasion. Despite the association of the stress-protective transcription factor heat shock factor 2 (HSF2) in cancer, its role in breast carcinogenesis has been poorly understood. This study investigates the expression and activity of HSF2 in human breast tumor samples and mouse in vivo xenografts, revealing a dynamic regulation of HSF2 during tumor progression.

The authors found that HSF2 expression, nuclear localization, and coexpression with the proliferation marker Ki67 are elevated in ductal carcinoma in situ (DCIS), indicating that HSF2 is involved in the early stages of tumor expansion. Interestingly, in mouse xenografts, HSF2 shifts from nuclear to cytoplasmic localization upon the transition from DCIS to invasive carcinoma. Using cell-based models, the team identified canonical transforming growth factor-β (TGF-β) signaling as the key regulator of HSF2. TGF-β–mediated downregulation of HSF2 allowed the acquisition of an invasive cell phenotype, a process that could be reversed by ectopic expression of HSF2.

These findings suggest that HSF2 functions as a stage-specific switch that controls the balance between proliferation and invasion in breast cancer.

Pessa JC, Paavolainen O, Hästbacka HSE, Puustinen MC, Da Silva AJ, Pihlström S, Gramolelli S, Boström P, Hartiala P, Peuhu E, Joutsen J, Sistonen L. HSF2 drives breast cancer progression by acting as a stage-specific switch between proliferation and invasion. Sci Adv. 2025 Sep 5;11(36):eady1289. doi: 10.1126/sciadv.ady1289.

For further reading, check out the Åbo Akademi press release and an exclusive interview with the authors in Åbo Underrättelser.

We are delighted to announce that Åbo Akademi University and Turku Bioscience have published a press release for our latest publication by Dr. Alejandro Da Silva titled “Nuclear talin-1 provides a bridge between cell adhesion and gene expression”. The findings were published in iScience and can be found here.

STRESS-SPECIFIC GENOME-WIDE PROGRAMS OF GENES AND ENHANCERS

Cells are exposed to various types of cytotoxic stress including oxidative stress, elevated temperatures and toxins. Surviving stressful conditions requires extensive reprogramming of transcription, which involves both upregulation and downregulation of genes. Heat shock has provided an excellent model to investigate how nascent transcription is regulated in cells exposed to proteotoxic stress. However, knowledge of transcriptional regulation during other types of stress is lacking. In this comprehensive study, the transcriptional reprogramming of genes and enhancers was analyzed upon two different types of stress, i.e. oxidative stress and heat shock by combining two different genome-wide analyses (PRO-seq and ChIP-seq). This approach allowed determining the target repertoire of both genes and enhancers that are regulated by two important stress-inducible transcription factors, HSF1 and HSF2.

This study revealed several exciting and surprising findings. HSF1 and HSF2 drive stress type-specific transcription programs, as their target genes in the oxidative stress response are different from the classical chaperone genes in the heat shock response. Moreover, besides functioning as promoter-binding transcription factors, both HSFs activate genes through enhancers in response to oxidative stress and heat shock. Intriguingly, in contrast to promoter-bound HSF1, which regulates classical chaperone genes, recruitment of HSF1 to enhancers is required for the induction of genes encoding proteins that reside in the plasma membrane. Taken together, this study highlights the unique property of HSFs being able to drive distinct transcription programs, through gene promoters and enhancers, depending on the type of stress. It is plausible that the capacity of HSFs to orchestrate transcription via enhancers is not limited to stress, since HSFs play important roles also in developmental and pathological processes, such as progression of cancer.

Himanen S.V., Puustinen M.C., Da Silva A.J., Vihervaara A. & Sistonen L. HSFs drive transcription of distinct genes and enhancers during oxidative stress and heat shock. Nucleic Acids Research 2022 June 10. DOI: 10.1093/nar/gkac493. Online ahead of print.

https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkac493/6605316

We are happy to announce that our latest publication in collaboration with Anniina Vihervaara, Assistant Professor in Gene Technology at KTH Royal Institute of Technology, is out now in Molecular Cell! A summary of the study can be found here.

Molecular Cell also released an interview with the authors that is available here.