Volume 31, No 1, Jan 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 1, January 2021: 5-16

REVIEW ARTICLE

Calreticulin and cancer

Jitka Fucikova^1,2 , Radek Spisek^1,2 , Guido Kroemer^3,4,5,6,7,* , Lorenzo Galluzz^{8,9,10,11,12,*}

¹Sotio, Prague, Czech Republic; 2 Department of Immunology, Charles University
²Faculty of Medicine and University Hospital Motol, Prague, Czech Republic
³Equipe labellisée par la Ligue contre le cancer, Centre de Recherche des Cordeliers, INSERM U1138, Université de Paris, Sorbonne Université, Paris, France
⁴Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France
⁵Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France
⁶Suzhou Institute for Systems Medicine, Chinese Academy of Sciences, Suzhou, Jiangsu, China
⁷Karolinska Institute, Deparment of Women’s and Children’s Health, Karolinska University Hospital, Stockholm, Sweden
⁸Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA
⁹Sandra and Edward Meyer Cancer Center, New York, NY, USA
¹⁰Caryl and Israel Englander Institute for Precision Medicine, New York, NY, USA
¹¹Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA
¹²Université de Paris, Paris, France
Correspondence: Guido Kroemer(kroemer@orange.fr)Lorenzo Galluzz(deadoc80@gmail.com)

Calreticulin (CALR) is an endoplasmic reticulum (ER)-resident protein involved in a spectrum of cellular processes. In healthy cells, CALR operates as a chaperone and Ca2+ buffer to assist correct protein folding within the ER. Besides favoring the maintenance of cellular proteostasis, these cell-intrinsic CALR functions support Ca2+-dependent processes, such as adhesion and integrin signaling, and ensure normal antigen presentation on MHC Class I molecules. Moreover, cancer cells succumbing to immunogenic cell death (ICD) expose CALR on their surface, which promotes the uptake of cell corpses by professional phagocytes and ultimately supports the initiation of anticancer immunity. Thus, loss-of-function CALR mutations promote oncogenesis not only as they impair cellular homeostasis in healthy cells, but also as they compromise natural and therapy-driven immunosurveillance. However, the prognostic impact of total or membrane-exposed CALR levels appears to vary considerably with cancer type. For instance, while genetic CALR defects promote pre-neoplastic myeloproliferation, patients with myeloproliferative neoplasms bearing CALR mutations often experience improved overall survival as compared to patients bearing wild-type CALR. Here, we discuss the context-dependent impact of CALR on malignant transformation, tumor progression and response to cancer therapy.

https://doi.org/10.1038/s41422-020-0383-9

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