Unveiling the dark side of glucose-regulated protein 78 (GRP78) in cancers and other human pathology: a systematic review

Amos Olalekan Akinyemi; Kendall Elizabeth Simpson; Sunday Faith Oyelere; Maria Nur; Chrispus Mutuku Ngule; Bolaji Charles Dayo Owoyemi; Vivian Adiila Ayarick; Felix Femi Oyelami; Oluwafunminiyi Obaleye; Dave Preston Esoe; Xiaoqi Liu; Zhiguo Li

doi:10.1186/s10020-023-00706-6

Unveiling the dark side of glucose-regulated protein 78 (GRP78) in cancers and other human pathology: a systematic review

Amos Olalekan Akinyemi
, Kendall Elizabeth Simpson
, Sunday Faith Oyelere
, Maria Nur
, Chrispus Mutuku Ngule
, Bolaji Charles Dayo Owoyemi
, Vivian Adiila Ayarick
, Felix Femi Oyelami
, Oluwafunminiyi Obaleye
, Dave Preston Esoe
, Xiaoqi Liu
, Zhiguo Li

Research output: Contribution to journal › Review article › peer-review

74 Scopus citations

Abstract

Glucose-Regulated Protein 78 (GRP78) is a chaperone protein that is predominantly expressed in the lumen of the endoplasmic reticulum. GRP78 plays a crucial role in protein folding by assisting in the assembly of misfolded proteins. Under cellular stress conditions, GRP78 can translocate to the cell surface (csGRP78) were it interacts with different ligands to initiate various intracellular pathways. The expression of csGRP78 has been associated with tumor initiation and progression of multiple cancer types. This review provides a comprehensive analysis of the existing evidence on the roles of GRP78 in various types of cancer and other human pathology. Additionally, the review discusses the current understanding of the mechanisms underlying GRP78's involvement in tumorigenesis and cancer advancement. Furthermore, we highlight recent innovative approaches employed in downregulating GRP78 expression in cancers as a potential therapeutic target.

Original language	English
Article number	112
Journal	Molecular Medicine
Volume	29
Issue number	1
DOIs	https://doi.org/10.1186/s10020-023-00706-6
State	Published - Dec 2023

Bibliographical note

Publisher Copyright:
© 2023, The Feinstein Institute for Medical Research.

Funding

The work was generously supported by the National Institutes of Health (NIH) (No. R01 CA266579 to Zhiguo Li) and partially supported by the UK CARES Career Development Program (No. P30ES026529) and the American Cancer Society (No. IRG 19–140-31).

Funders	Funder number
UK-CARES	P30ES026529
National Institutes of Health (NIH)	R01 CA266579
American Cancer Society-Michigan Cancer Research Fund	IRG 19–140-31

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

BiP
Cancer
Chaperon
Disease
ER stress
ERAD
GRP78
URP

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics
Genetics(clinical)

Access to Document

10.1186/s10020-023-00706-6

Cite this

Akinyemi, A. O., Simpson, K. E., Oyelere, S. F., Nur, M., Ngule, C. M., Owoyemi, B. C. D., Ayarick, V. A., Oyelami, F. F., Obaleye, O., Esoe, D. P., Liu, X., & Li, Z. (2023). Unveiling the dark side of glucose-regulated protein 78 (GRP78) in cancers and other human pathology: a systematic review. Molecular Medicine, 29(1), Article 112. https://doi.org/10.1186/s10020-023-00706-6

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abstract = "Glucose-Regulated Protein 78 (GRP78) is a chaperone protein that is predominantly expressed in the lumen of the endoplasmic reticulum. GRP78 plays a crucial role in protein folding by assisting in the assembly of misfolded proteins. Under cellular stress conditions, GRP78 can translocate to the cell surface (csGRP78) were it interacts with different ligands to initiate various intracellular pathways. The expression of csGRP78 has been associated with tumor initiation and progression of multiple cancer types. This review provides a comprehensive analysis of the existing evidence on the roles of GRP78 in various types of cancer and other human pathology. Additionally, the review discusses the current understanding of the mechanisms underlying GRP78's involvement in tumorigenesis and cancer advancement. Furthermore, we highlight recent innovative approaches employed in downregulating GRP78 expression in cancers as a potential therapeutic target.",

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author = "Akinyemi, \{Amos Olalekan\} and Simpson, \{Kendall Elizabeth\} and Oyelere, \{Sunday Faith\} and Maria Nur and Ngule, \{Chrispus Mutuku\} and Owoyemi, \{Bolaji Charles Dayo\} and Ayarick, \{Vivian Adiila\} and Oyelami, \{Felix Femi\} and Oluwafunminiyi Obaleye and Esoe, \{Dave Preston\} and Xiaoqi Liu and Zhiguo Li",

note = "Publisher Copyright: {\textcopyright} 2023, The Feinstein Institute for Medical Research.",

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month = dec,

doi = "10.1186/s10020-023-00706-6",

language = "English",

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AU - Nur, Maria

AU - Ngule, Chrispus Mutuku

AU - Owoyemi, Bolaji Charles Dayo

AU - Ayarick, Vivian Adiila

AU - Oyelami, Felix Femi

AU - Obaleye, Oluwafunminiyi

AU - Esoe, Dave Preston

AU - Liu, Xiaoqi

AU - Li, Zhiguo

PY - 2023/12

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AB - Glucose-Regulated Protein 78 (GRP78) is a chaperone protein that is predominantly expressed in the lumen of the endoplasmic reticulum. GRP78 plays a crucial role in protein folding by assisting in the assembly of misfolded proteins. Under cellular stress conditions, GRP78 can translocate to the cell surface (csGRP78) were it interacts with different ligands to initiate various intracellular pathways. The expression of csGRP78 has been associated with tumor initiation and progression of multiple cancer types. This review provides a comprehensive analysis of the existing evidence on the roles of GRP78 in various types of cancer and other human pathology. Additionally, the review discusses the current understanding of the mechanisms underlying GRP78's involvement in tumorigenesis and cancer advancement. Furthermore, we highlight recent innovative approaches employed in downregulating GRP78 expression in cancers as a potential therapeutic target.

KW - BiP

KW - Cancer

KW - Chaperon

KW - Disease

KW - ER stress

KW - ERAD

KW - GRP78

KW - URP

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DO - 10.1186/s10020-023-00706-6

M3 - Review article

C2 - 37605113

AN - SCOPUS:85168459940

SN - 1076-1551

VL - 29

JO - Molecular Medicine

JF - Molecular Medicine

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ER -

Unveiling the dark side of glucose-regulated protein 78 (GRP78) in cancers and other human pathology: a systematic review

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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Cite this