Functional roles of calreticulin in cancer biology.
Calreticulin is a highly conserved endoplasmic reticulum chaperone protein which participates in various cellular processes. It was first identified as a Ca(2+)-binding protein in 1974. Accumulated evidences indicate that calreticulin has great impacts for the development of different cancers and the effect of calreticulin on tumor formation and progression may depend on cell types and clinical stages. Cell surface calreticulin is considered as an "eat-me" signal and promotes phagocytic uptake of cancer cells by immune system. Moreover, several reports reveal that manipulation of calreticulin levels profoundly affects cancer cell proliferation and angiogenesis as well as differentiation. In addition to immunogenicity and tumorigenesis, interactions between calreticulin and integrins have been described during cell adhesion, which is an essential process for cancer metastasis. Integrins are heterodimeric transmembrane receptors which connect extracellular matrix and intracellular cytoskeleton and trigger inside-out or outside-in signaling transduction. More and more evidences reveal that proteins binding to integrins might affect integrin-cytoskeleton interaction and therefore influence ability of cell adhesion. Here, we reviewed the biological roles of calreticulin and summarized the potential mechanisms of calreticulin in regulating mRNA stability and therefore contributed to cancer metastasis.
Department of Life Science, National Taiwan University, Taipei 106, Taiwan ; Department of Radiology, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan ; Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
Yi-Chien
YC
Lu
Department of Life Science, National Taiwan University, Taipei 106, Taiwan ; Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
Wen-Chin
WC
Weng
Department of Life Science, National Taiwan University, Taipei 106, Taiwan ; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei 116, Taiwan ; Center for Biotechnology, National Taiwan University, Taipei 116, Taiwan ; Angiogenesis Research Center, National Taiwan University, Taipei 116, Taiwan.
Hsinyu
H
Lee
D002118:Calcium / Q000378:metabolism; D037282:Calreticulin / Q000235:genetics* / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics*; D002448:Cell Adhesion / Q000235:genetics*; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000235:genetics; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics
C576483:CALR protein, human; D037282:Calreticulin; D002118:Calcium