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Emerging Roles of Calreticulin in Cancer: Implications for Therapy

[ Vol. 19 , Issue. 4 ]

Author(s):

Kavya Venkateswaran, Amit Verma, Anant Narayan Bhatt, Anju Shrivastava, Kailash Manda, Hanumantharao G. Raj, Ashok Prasad, Christophe Len, Virinder S. Parmar and Bilikere S. Dwarakanath*   Pages 344 - 357 ( 14 )

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.

Keywords:

Calreticulin, immunogenic cell death, danger-associated molecular patterns, protein acetylation, polyphenolic acetates, calreticulin transacetylase, cancer therapy.

Affiliation:

Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Marg, Lucknow Road, Delhi 110054, Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Marg, Lucknow Road, Delhi 110054, Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Marg, Lucknow Road, Delhi 110054, Department of Zoology, University of Delhi, Delhi 110007, Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Marg, Lucknow Road, Delhi 110054, Department of Biochemistry, VP Chest Institute, University of Delhi, Delhi 110007, Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, Department of Chemistry, University of Hull, Hull HU6 7RX, Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, Central Research Facility, Sri Ramachandra University, Porur, Chennai 600116

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