期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 78, 期 9, 页码 4069-4083出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-021-03764-3
关键词
Extracellular; Chaperones; Heat shock proteins; Tumour microenvironment; Cancer hallmarks
资金
- Universita degli Studi di Torino
- Digital Technology For Lung Cancer Treatment (DEFLeCT)
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [24216]
Heat shock proteins play crucial roles in cellular homeostasis and stress response, with extracellular heat shock proteins potentially contributing to cancer development and metastasis by supporting cancer hallmarks and modulating the tumor microenvironment.
In addition to exerting several essential house-keeping activities in the cell, heat shock proteins (HSPs) are crucial players in a well-structured molecular program activated in response to stressful challenges. Among the different activities carried out by HSPs during emergency, they reach the extracellular milieu, from where they scout the surroundings, regulate extracellular protein activity and send autocrine and paracrine signals. Cancer cells permanently experience stress conditions due to their altered equilibrium and behaviour, and constantly secrete heat shock proteins as a result. Other than supporting anti-tumour immunity, extracellular heat shock proteins (eHSPs), can also exacerbate cancer cell growth and malignancy by sustaining different cancer hallmarks. eHSPs are implicated in extracellular matrix remodelling, resistance to apoptosis, promotion of cell migration and invasion, induction of epithelial to mesenchymal transition, angiogenesis and activation of stromal cells, supporting ultimately, metastasis dissemination. A broader understanding of eHSP activity and contribution to tumour development and progression is leading to new opportunities in the diagnosis and treatment of cancer.
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