Abstrakti
Extracellular vesicles (EVs) are key mediators of intercellular communication
and transport diverse cargo such as proteins, lipids, and nucleic acids. They
are involved in various physiological and pathological processes, including
immune responses, tissue repair, neurodegenerative diseases, and cancer
progression. In cancer, EVs may contribute to tumor invasion and metastasis
by remodeling the extracellular matrix, promoting angiogenesis, and
modulating the immune response. Despite their importance, EV research
faces challenges due to the complexity of biological systems and the technical
demands of isolation and characterization.
Heat shock factors (HSFs), particularly HSF1 and HSF2, have garnered
attention for their roles in cellular stress responses. While HSF1 is well-
known for inducing heat shock proteins, the functions of HSF2 have been less
clear. Recent studies reveal critical roles of HSF2 in development,
differentiation, cellular homeostasis, and cancer.
This thesis explores the impact of EVs and HSF2 on cancer and cellular stress
responses. The first study examined cancer cell invasion and its impact on EV
protein profiles, discovering significant alterations in EV amounts, surface
charge, and protein cargo content, with unique proteins implicated in tumor
growth and invasion. The second study focused on HSF2's role in proteotoxic
stress response, using HSF2 knockout cell lines and RNA sequencing to reveal
HSF2's regulation of the cadherin superfamily, crucial for maintaining cell-cell
adhesion. The third study presented the first interactome analysis of HSF2 in
mouse testis and human PC3 cells, identifying and validating novel
interactions between HSF2 and cell adhesion proteins, particularly talin 1,
through co-immunoprecipitation and mass spectrometry. These findings
provide new insights into the molecular mechanisms of cancer progression
and cellular stress response, highlighting potential biomarkers and
therapeutic targets for cancer treatment.
and transport diverse cargo such as proteins, lipids, and nucleic acids. They
are involved in various physiological and pathological processes, including
immune responses, tissue repair, neurodegenerative diseases, and cancer
progression. In cancer, EVs may contribute to tumor invasion and metastasis
by remodeling the extracellular matrix, promoting angiogenesis, and
modulating the immune response. Despite their importance, EV research
faces challenges due to the complexity of biological systems and the technical
demands of isolation and characterization.
Heat shock factors (HSFs), particularly HSF1 and HSF2, have garnered
attention for their roles in cellular stress responses. While HSF1 is well-
known for inducing heat shock proteins, the functions of HSF2 have been less
clear. Recent studies reveal critical roles of HSF2 in development,
differentiation, cellular homeostasis, and cancer.
This thesis explores the impact of EVs and HSF2 on cancer and cellular stress
responses. The first study examined cancer cell invasion and its impact on EV
protein profiles, discovering significant alterations in EV amounts, surface
charge, and protein cargo content, with unique proteins implicated in tumor
growth and invasion. The second study focused on HSF2's role in proteotoxic
stress response, using HSF2 knockout cell lines and RNA sequencing to reveal
HSF2's regulation of the cadherin superfamily, crucial for maintaining cell-cell
adhesion. The third study presented the first interactome analysis of HSF2 in
mouse testis and human PC3 cells, identifying and validating novel
interactions between HSF2 and cell adhesion proteins, particularly talin 1,
through co-immunoprecipitation and mass spectrometry. These findings
provide new insights into the molecular mechanisms of cancer progression
and cellular stress response, highlighting potential biomarkers and
therapeutic targets for cancer treatment.
| Alkuperäiskieli | Englanti |
|---|---|
| Valvoja/neuvonantaja |
|
| Julkaisupaikka | Åbo |
| Kustantaja | |
| Painoksen ISBN | 978-952-12-4442-1 |
| Sähköinen ISBN | 978-952-12-4443-8 |
| Tila | Julkaistu - 2024 |
| OKM-julkaisutyyppi | G5 Tohtorinväitöskirja (artikkeli) |