Heat shock proteins and cancer: The FoxM1 connection

Zahra Alimardan; Maryam Abbasi; Farshid Hasanzadeh; Mahmud Aghaei; Ghadamali Khodarahmi; Khosrow Kashfi

doi:10.1016/j.bcp.2023.115505

Heat shock proteins and cancer: The FoxM1 connection

Biochem Pharmacol. 2023 May:211:115505. doi: 10.1016/j.bcp.2023.115505. Epub 2023 Mar 15.

Authors

Zahra Alimardan¹, Maryam Abbasi², Farshid Hasanzadeh³, Mahmud Aghaei⁴, Ghadamali Khodarahmi⁵, Khosrow Kashfi⁶

Affiliations

¹ Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Pharmacology, School of Medicine, Arak University of Medical Sciences, Arak, Iran.
² Department of Medicinal Chemistry, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
³ Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
⁴ Department of Biochemistry, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.
⁵ Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran; Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address: khodarahmi@pharm.mui.ac.ir.
⁶ Department of Molecular, Cellular and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, NY, USA; Graduate Program in Biology, City University of New York Graduate Center, NY, USA. Electronic address: kashfi@med.cuny.edu.

Abstract

Heat shock proteins (Hsp) and FoxM1 have significant roles in carcinogenesis. According to their relative molecular weight, Hsps are divided into Hsp110, Hsp90, Hsp70, Hsp60, Hsp40, and small Hsps. Hsp70 can play essential functions in cancer initiation and is overexpressed in several human cancers. Hsp70, in combination with cochaperones HIP and HOP, refolds partially denatured proteins and acts as a cochaperone for Hsp90. Also, Hsp70, in combination with BAG3, regulates the FoxM1 signaling pathway. FoxM1 protein is a transcription factor of the Forkhead family that is overexpressed in most human cancers and is involved in many cancers' development features, including proliferation, migration, invasion, angiogenesis, metastasis, and resistance to apoptosis. This review discusses the Hsp70, Hsp90, and FoxM1 structure and function, the known Hsp70 cochaperones, and Hsp70, Hsp90, and FoxM1 inhibitors.

Keywords: Cancer; Cochaperones; FoxM1; Hsp70; Hsp90; Inhibitors.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / metabolism
Apoptosis Regulatory Proteins / metabolism
Forkhead Box Protein M1 / genetics
Forkhead Box Protein M1 / metabolism
HSP40 Heat-Shock Proteins / metabolism
HSP70 Heat-Shock Proteins / metabolism
HSP90 Heat-Shock Proteins / metabolism
Heat-Shock Proteins* / metabolism
Humans
Neoplasms*

Substances

Heat-Shock Proteins
HSP70 Heat-Shock Proteins
HSP90 Heat-Shock Proteins
HSP40 Heat-Shock Proteins
BAG3 protein, human
Adaptor Proteins, Signal Transducing
Apoptosis Regulatory Proteins
FOXM1 protein, human
Forkhead Box Protein M1

Abstract

Publication types

MeSH terms

Substances

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