The Interplay between Heat Shock Proteins and Cancer Pathogenesis: A Novel Strategy for Cancer Therapeutics
by
, , , ,
Prathap Somu
1,†
,
Sonali Mohanty
2
,
Nagaraj Basavegowda
3,†
,
Akhilesh Kumar Yadav
4,5,
Subhankar Paul
2,* and
Kwang-Hyun Baek
3,*
1
Department of Biotechnology and Chemical Engineering, School of Civil & Chemical Engineering, Manipal University Jaipur, Dehmi Kalan, Jaipur 303007, India
2
Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela 769008, India
3
Department of Biotechnology, Yeungnam University, Gyeongsan 38451, Republic of Korea
4
Department of Environmental Engineering and Management, Chaoyang University of Technology, Taichung 413310, Taiwan
5
Department of Bioengineering, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai 602105, India
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2024, 16(3), 638; https://doi.org/10.3390/cancers16030638
Submission received: 15 January 2024
/
Revised: 29 January 2024
/
Accepted: 30 January 2024
/
Published: 1 February 2024
(This article belongs to the Section Molecular Cancer Biology)
Simple Summary
Heat shock proteins (HSPs) are extensively distributed throughout cells. They play a crucial role as molecular chaperones and regulate various cellular processes, such as metabolism, growth, differentiation, cell signaling, and programmed cell death. However, in cancers, HSPs are frequently overexpressed and associated with tumor advancement and metastasis, as well as in acquiring drug resistance against chemotherapeutic agents, leading to poor prognosis. Thus, the expression of HSPs can be modulated to imitate the cellular response against cancer cells by targeting the tumor microenvironment through different mechanisms. For instance, HSPs bind to antigens (peptides) associated with tumors, forming a complex that is easily recognized as an antigen-presenting cell (APC), leading to specific antitumor responses. This review summarizes and discusses recent advances, perspectives, and involvement of HSPs, including small and large HSPs, as well as the molecular mechanisms underlying tumor progression and metastasis. This study may offer new insights into the development of safer and more effective anticancer therapeutics.
Abstract
Heat shock proteins (HSPs) are developmentally conserved families of protein found in both prokaryotic and eukaryotic organisms. HSPs are engaged in a diverse range of physiological processes, including molecular chaperone activity to assist the initial protein folding or promote the unfolding and refolding of misfolded intermediates to acquire the normal or native conformation and its translocation and prevent protein aggregation as well as in immunity, apoptosis, and autophagy. These molecular chaperonins are classified into various families according to their molecular size or weight, encompassing small HSPs (e.g., HSP10 and HSP27), HSP40, HSP60, HSP70, HSP90, and the category of large HSPs that include HSP100 and ClpB proteins. The overexpression of HSPs is induced to counteract cell stress at elevated levels in a variety of solid tumors, including anticancer chemotherapy, and is closely related to a worse prognosis and therapeutic resistance to cancer cells. HSPs are also involved in anti-apoptotic properties and are associated with processes of cancer progression and development, such as metastasis, invasion, and cell proliferation. This review outlines the previously mentioned HSPs and their significant involvement in diverse mechanisms of tumor advancement and metastasis, as well as their contribution to identifying potential targets for therapeutic interventions.
