Calreticulin (CRT) is a 46 kDa highly conserved protein initially identified as calregulin, a prominent Ca2+-binding protein of the endoplasmic reticulum (ER). Subsequent studies have established that CRT functions in the ER’s protein folding response and Ca2+homeostatic mechanisms. An ER retention signal on the carboxyl terminus of CRT suggested that CRT was restricted to the ER. However, the identification of CRT in the nucleus and cytosol has established that CRT is a multi-compartmental, multifunctional protein. CRT also plays an important role in cancer progression. Most recently, CRT was identified on the cell surface and shown to be a potent ‘eat-me’ signal that plays a key role in the uptake of apoptotic and viable cancer cells by phagocytes. Elevated CRT exposure on the outer leaflet of cancer cells has been linked with anticancer immunity and superior therapeutic outcomes in patients with non-small cell lung carcinoma, colorectal carcinoma, acute myeloid leukemia, ovarian cancer, and high-grade serous carcinomas. Mutations in the CRT gene have been identified in a subset of patients with myeloproliferative neoplasms. The most recent studies from our laboratory have revealed a new and significant function for extracellular CRT as a plasminogen receptor. This discovery has profound implications for our understanding of the role of CRT in myeloproliferative neoplasms, specifically, essential thrombocythemia.
钙网蛋白（CRT）是一种46 kDa的高度保守蛋白，最初被鉴定为钙调节蛋白，是内质网（ER）中一种重要的Ca2+结合蛋白。后续研究证实，CRT在内质网的蛋白质折叠反应和Ca2+稳态机制中发挥作用。CRT羧基末端的ER滞留信号表明其通常局限于内质网内。然而，在细胞核和细胞质中鉴定出的CRT证实了它是一种多区室、多功能的蛋白质。CRT在癌症进展中也扮演着重要角色。最近研究发现，CRT存在于细胞表面，并被证实是一种有效的“吞噬我”信号，在吞噬细胞摄取凋亡及存活的癌细胞过程中起关键作用。癌细胞外膜表面CRT暴露水平的升高与非小细胞肺癌、结直肠癌、急性髓系白血病、卵巢癌及高级别浆液性癌患者的抗癌免疫反应及更佳的治疗效果相关。在部分骨髓增殖性肿瘤患者中已鉴定出CRT基因突变。我们实验室的最新研究揭示了细胞外CRT作为纤溶酶原受体的全新重要功能。这一发现对我们理解CRT在骨髓增殖性肿瘤（特别是原发性血小板增多症）中的作用具有深远意义。
Calreticulin—From the Endoplasmic Reticulum to the Plasma Membrane—Adventures of a Wandering Protein
肿瘤(癌症)患者之家