Calreticulin and Cancer
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REVIEW
Calreticulin and Cancer Mohammadreza Zamanian & Abhi Veerakumarasivam & Syahril Abdullah & Rozita Rosli
Received: 28 November 2011 / Accepted: 21 December 2012 / Published online: 8 February 2013 # Arányi Lajos Foundation 2013
Abstract Calreticulin (CRT) as a multi-functional endoplasmic reticulum protein is involved in a spectrum of cellular processes which ranges from calcium homeostasis and chaperoning to cell adhesion and finally malignant formation and progression. Previous studies have shown a contributing role for CRT in a range of different cancers. This present review will focus on the possible roles of CRT in the progression of malignant proliferation and the mechanisms involved in its contribution to cancer invasion. Keywords Calreticulin . Endoplasmic reticulum . Cancer . Malignant progression . Invasion . Metastasis
Calreticulin Calreticulin (CRT), as a multifunctional protein resides in the endoplasmic reticulum (ER) [1] as well as other cellular compartments such as the cell membrane, cytoplasm and nucleus [2]. The CRT structure includes the N and C terminals and three different domains [3] (Fig. 1). The N-terminal is a cleavable amino acid signal sequence while the C-terminal includes a KDEL ER retrieval signal. These specific sequences of amino acids are responsible for the different functions of CRT such as chaperoning [4], integrin binding [5], attachment to steroid hormone receptors [6], Ca2+ binding and interacting with other chaperones like calnexin [7].
Biological Functions M. Zamanian : A. Veerakumarasivam : S. Abdullah : R. Rosli Genetic Medicine Research Center, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor Darul Ehsan, Malaysia S. Abdullah : R. Rosli (*) UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400, Serdang, Selangor Darul Ehsan, Malaysia e-mail: [email protected] R. Rosli e-mail: [email protected] M. Zamanian Medical Genetics Group, Genetics Department, Reproductive Biomedicine Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran A. Veerakumarasivam Perdana University Graduate School of Medicine, Perdana University, Serdang 43400, Selangor Darul Ehsan, Malaysia
Molecular chaperoning and calcium homeostasis are two main physiological role of CRT inside the ER. It is also present on the membrane of other cellular organelles, cell surface and in the extracellular environment where it contributes to different physiological and pathological roles such as cell adhesion, transcriptional activities and gene expression regulation as well as recognition and elimination of apoptotic cells [8, 9]. Finally, new roles of CRT in the extracellular space such as the involvement in cutaneous wound healing [10] and possible diagnostic applications of CRT in blood [11] or urine [12] have emerged.
Transcriptional Regulation of CRT The human CRT gene is located on chromosome 19 [13] and its promoter region includes multiple regulatory sites such as AP-1, AP-2 and GC rich are
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