Abstract
The lectin chaperones calreticulin (CALR) and calnexin (CANX), together with their co-chaperone PDIA3, are increasingly implicated in studies of human cancers in roles that extend beyond their primary function as quality control facilitators of protein folding within the endoplasmic reticulum (ER). Led by the discovery that cell surface CALR functions as an immunogen that promotes anti-tumour immunity, studies have now expanded to include their potential uses as prognostic markers for cancers, and in regulation of oncogenic signaling that regulate such diverse processes including integrin-dependent cell adhesion and migration, proliferation, cell death and chemotherapeutic resistance. The diversity stems from the increasing recognition that these proteins have an equally diverse spectrum of subcellular and extracellular localization, and which are aberrantly expressed in tumour cells. This review describes key foundational discoveries and highlight recent findings that further our understanding of the plethora of activities mediated by CALR, CANX and PDIA3.
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Abbreviations
- CAM-DR:
-
Cell adhesion mediated drug resistance
- CALR:
-
Calreticulin, also known as calregulin, CRT, CRP55, CaBP3 and ERp60
- CANX:
-
Calnexin, also known as CNX, IP90 and P90
- DAMP:
-
Damage associated molecular patterns
- ER:
-
Endoplasmic reticulum
- PDIA3:
-
Protein disulfide isomerase A3, also known as ERp57, ER60, GRP57, GRP58
- ERK:
-
Extracellular signal regulated kinase
- ICD:
-
Immunogenic cell death
- MAPK:
-
Mitogen activated protein kinase
- STAT3:
-
Signal transducer and activator of transcription 3
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Acknowledgments
Research conducted in CJL’s laboratory was supported by grants from the Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Canadian Cancer Society Research Institute and the Leukemia and Lymphoma Society of Canada. We also acknowledge additional funding received from the Michael Cuccione Foundation for Childhood Cancer Research and the BC Children’s Hospital Foundation.
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Lam, S.T.T., Lim, C.J. (2021). Cancer Biology of the Endoplasmic Reticulum Lectin Chaperones Calreticulin, Calnexin and PDIA3/ERp57. In: Agellon, L.B., Michalak, M. (eds) Cellular Biology of the Endoplasmic Reticulum . Progress in Molecular and Subcellular Biology, vol 59. Springer, Cham. https://doi.org/10.1007/978-3-030-67696-4_9
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