title: Emerging Roles of Calreticulin in Cancer: Implications for Therapy.
abstract: Calreticulin (CRT), initially identified as a ubiquitous calcium-binding protein in the endoplasmic reticulum, has emerged as a multifunctional protein with roles in calcium homeostasis, molecular chaperoning and cell adhesion. Emerging evidence suggests its involvement in tumorigenesis facilitating proliferation, migration, and adhesion. CRT translocated to the cell surface (ecto-CRT) serves as a phagocytic signal for immunogenic cell death (ICD) mediated through dendritic cells (DCs) and cytotoxic T-cell activation thereby making tumors susceptible to immunotherapy-based anti-cancer strategies. CRT is now regarded as one of the most potent danger-associated molecular patterns (DAMPs) with the ecto-CRT triggering restoration of homeostasis by immune stimulation. A recently identified novel transacetylase activity of CRT adds a new dimension to its multi-faceted involvement in cancer by virtue of polyphenolic acetates (PA): CRT transacetylase (CRTase) system which results in hyperacetylation of target proteins, thereby mimicking the effects of Histone deacetylase inhibitors (HDACi). Since protein acetylation is one of the crucial post-translational modifications (PTMs) influencing the epigenetic regulation and signal transduction, CRT can be a potential target for developing anticancer therapeutics and preventive strategies by employing pharmacologically compatible semi-synthetic acetyl donors like polyphenolic acetates and other agents.
authors.affiliation: Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Marg, Lucknow Road, Delhi 110054, India.|Department of Zoology, University of Delhi, Delhi 110007, India.
authors.forename: Kavya
authors.initials: K
authors.lastname: Venkateswaran
authors.affiliation: Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Marg, Lucknow Road, Delhi 110054, India.|Armed Forces Radiobiology Research Institute, Bethesda, Maryland, MD, United States of America.
authors.forename: Amit
authors.initials: A
authors.lastname: Verma
authors.affiliation: Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Marg, Lucknow Road, Delhi 110054, India.
authors.forename: Anant Narayan
authors.initials: AN
authors.lastname: Bhatt
authors.affiliation: Department of Zoology, University of Delhi, Delhi 110007, India.
authors.forename: Anju
authors.initials: A
authors.lastname: Shrivastava
authors.affiliation: Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Marg, Lucknow Road, Delhi 110054, India.
authors.forename: Kailash
authors.initials: K
authors.lastname: Manda
authors.affiliation: Department of Biochemistry, VP Chest Institute, University of Delhi, Delhi 110007, India.
authors.forename: Hanumantharao G
authors.initials: HG
authors.lastname: Raj
authors.affiliation: Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Prasad
authors.affiliation: Sorbonne Universites, Universite de Technologie de Compiegne (UTC), Ecole Superieure de Chimie Organique et Minerale (ESCOM), CS 60319, 60203 Compiegne Cedex, France.|Department of Chemistry, University of Hull, Hull HU6 7RX, United Kingdom.
authors.forename: Christophe
authors.initials: C
authors.lastname: Len
authors.affiliation: Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India.|Sorbonne Universites, Universite de Technologie de Compiegne (UTC), Ecole Superieure de Chimie Organique et Minerale (ESCOM), CS 60319, 60203 Compiegne Cedex, France.
authors.forename: Virinder S
authors.initials: VS
authors.lastname: Parmar
authors.affiliation: Central Research Facility, Sri Ramachandra University, Porur, Chennai 600116, India.|Shanghai Proton and Heavy Ion Center, Pudong, Shanghai 201321, China.
authors.forename: Bilikere S
authors.initials: BS
authors.lastname: Dwarakanath
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D037282:Calreticulin / Q000737:chemistry* / Q000494:pharmacology*; D016923:Cell Death; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D004721:Endoplasmic Reticulum / Q000378:metabolism; D044127:Epigenesis, Genetic; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D037282:Calreticulin; D000123:Acetyltransferases; C539012:calreticulin transacetylase, human
keywords: Calreticulin; calreticulin transacetylase; cancer therapy.; danger-associated molecular patterns; immunogenic cell death; polyphenolic acetates; protein acetylation