Enhanced Expression of the Protein Kinase Substrate Annexin I in Human Hepatocellular Carcinoma

Abstract

and chromobindins. 15 AXs were first described as glucocortiAnnexin (AX) constitutes a new family of Ca 2/ -depencoid-inducible inhibitory proteins of phospholipase A 2 . 13,14 dent membrane-binding proteins; 13 of them have been These proteins possess four or eight conserved 70 amino acid described. Among these, annexin-I (AX-I) has displayed repeats, which comprise the core domain, where Ca 2/ -and many biological functions in vitro. Its actual role in vivo, phospholipid-binding functions are located. Annexins have however, remains unknown. We already reported that unique N-terminal tails that vary in length and sequence. 3,15 AX-I was expressed in proliferating (regenerating) hepaSubsequent studies have shown that AX-I (molecular weight, tocytes at both protein and messenger RNA (mRNA) lev-35 kd) is identical to the Ca 2/ -dependent phospholipid-and els. The role of AX-I in human hepatocellular carcinoma actin-binding protein. 2,16,17 In particular, AX-I is the major (HCC) remains obscure. In this study, the amounts of substrate for epidermal growth factor receptor (EGFR) ki-AX-I at protein and mRNA levels, as well as its localizanase, [17][18][19][20][21][22][23] and also for serine/threonine kinases such as protion, have been determined in the normal human liver, tein kinase C. 24 Various AXs have been implicated in cellular chronic hepatitis liver, and nontumorous and tumorous processes, including modulation of phospholipase A 2 activity portions of HCC. AX-I was rarely found in normal and and inflammation, 13,14,25 exocytosis, 26-28 differentiation, 29,30 chronic liver tissues, whereas it is overexpressed at both proliferation, 31-33 blood coagulation, 34 immune response, 35 the transcriptional and translational levels in tumorous membrane-cytoskeletal linkage, 36 and intracellular signal and nontumorous regions of HCC. In addition, more AXtransduction. 37,38 Although the conservation of AXs during I was expressed in the tumorous portion than the nontuevolution argues strongly for their important physiological morous portion of HCC. AX-I was present in the hepatoroles, this notion remains confusing and controversial. cytes and HCC cells, localized mainly in the cytoplasm.The in vivo phosphorylation of AX-I is induced by stimula-AX-I was overexpressed in poorly differentiated cancer tion with EGFR, and it profoundly affects its Ca 2/ requirecells. Furthermore, AX-I was tyrosine-phosphorylated in ment for phospholipid binding. [18][19][20][21]23 Although these results HCC. We also found that some of the AX-I-positive hepaare consistent with the roles of AX-I in cell transformation tocytes in the nontumorous tissues were derived from a and stimulation of cell growth, 32 such roles have yet to be particular subset of parenchymal cells (stem or oval delineated. We earlier showed that AX-I levels increase in cells). These results indicate that AX-I plays an improliferative (or regenerative) hepatocytes, suggesting that portant role in the malignant transformation process it plays a specific role in this event....

An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer

“…Prior studies have demonstrated increased expression of annexin I and͞or II in different tumor types (36)(37)(38)(39)(40). Thus, the extent to which annexin II autoantibodies may occur in tumor types other than lung cancer requires further investigation, in particular, in cancer types in which increased annexin II has been observed previously, as in the case of glioblastoma multiforme (39), pancreatic cancer (40), and acute premyelocytic leukemia (41).…”

Annexin-1 Downregulation Is Associated with Clinical Outcome in Chinese Patients with Hilar Cholangiocarcinoma

“…ANXA1 is a novel biomarker in predicting patients' clinical outcome. However, its expression in cancer remains controversial because it is reduced in certain cancers [12][13][14][15][16]36] , but increased in other cancer types [5,[7][8][9][10] . In the present study, we observed that ANXA1 was downregulated in hilar cholangiocarcinoma specimens compared with normal tissues.…”

“…The following studies revealed that ANXA1 also played a critical role in regulating cell proliferation, apoptosis, and carcinogenesis. Previous studies showed that ANXA1 expression was increased in pancreatic [7] , hepatic [8] , glial [9] and esophageal and esophagogastric junction adenocarcinomas [5,10] . However, recent studies revealed that ANXA1 expression was markedly decreased in esophageal [11] , gastric [12] , thyroid [13] , nasopharyngeal [14] , and breast carcinomas [15,16] , and correlated with tumor differentiation, metastasis, and poor outcome.…”

Expression of Annexin A3 in Primary Cultured Parenchymal Rat Hepatocytes and Inhibition of DNA Synthesis by Suppression of Annexin A3 Expression Using RNA Interference

“…30) AnxA1 increased in the proliferative hepatocytes after carbon tetrachloride-induced rat liver damage or a partial hepatectomy and in hepatocellullar carcinoma tissue. 31,32) Although the mechanism of action of AnxA3 on DNA synthesis is presently uncertain, the target of AnxA3 may be a common signal transduction pathway, and not necessarily a constitutive or growth factor-mediated one, because the suppression of AnxA3 expression using RNAi not only inhibited the control of DNA synthesis, but also EGF-or HGF-stimulated DNA synthesis, almost to a similar level. In this respect, the findings described below may be relevant to speculations on the mechanism of action of AnxA3 on DNA synthesis.…”