Differential expression of Axl in hepatocellular carcinoma and correlation with tumor lymphatic metastasis
Authors: Lili Jiang
Jianing Zhang
Li Jia
Yongfu Zhao
Changgong Jin
Guang Yang
Ling He
Journal: Molecular Carcinogenesis (2010)
Discipline: CLINICAL MEDICINE
Keywords: Protein kinases; tumor development; progression; signal transduction enzymes; therapeutic intervention
Affiliations: College of Laboratory Medicine, Dalian Medical University, Liaoning Province, China.

Abstract:  Protein kinases play important roles in tumor development and progression. A variety of members of the signal transduction enzymes serve as targets for therapeutic intervention in cancer. The dysregulation of Axl receptor and its ligand growth arrest-specific 6 (Gas6) is implicated in the pathogenesis of several cancers. In this study, the differential expressions of Axl were investigated in mouse hepatocarcinoma cell lines Hca-F and Hca-P, which have high- and low-metastatic potential to lymph nodes. Experimental inhibition of Axl by siRNA assessed further the metastatic potential of Axl. The results showed that down-regulation of Axl expression attenuated Hca-F cells proliferation, migration, and invasion in vitro, as well as inhibited metastasis to peripheral lymph nodes in vivo. Further analysis demonstrated that the addition of exogenous Gas6 mediated the migration and invasion of Hca-F cells both in vitro and in vivo through Axl. Furthermore, Gas6 stimulation of Axl in Hca-F cells resulted primarily in the down-regulation of Cyr61, a member of the CCN protein family involved in tumor progression. These data suggest that Axl acts as a tumor lymphatic metastasis-associated gene, and may function partly through the regulation of Cyr61. 

Retracted: No

PubPeer comments:
 Figure 2D and E. ![] Left-hand panel of D overlaps with Fig 2 of  CD147 depletion down-regulates matrix metalloproteinase-11, vascular endothelial growth factor-A expression and the lymphatic metastasis potential of murine hepatocarcinoma Hca-F cells [(Jia et al. 2007)] . ![file] Middle panel of D overlaps with Fig 3B of  Axl glycosylation mediates tumor cell proliferation, invasion and lymphatic metastasis in murine hepatocellular carcinoma [(Jia et al 2012)] . ![file] Right-hand panel of D and lefthand, righthand panels of E overlap with Fig 4B of  Modification of glycosylation mediates the invasive properties of murine hepatocarcinoma cell lines to lymph nodes [(Zhang et al 2013)] . ![] Some of the matches involve additional cells in one or other partner, with the melancholy implication that images have been manipulated. , 
 Figure 3C: ![] Had previously appeared (differently identified) as 2(B) of  CD147 regulates vascular endothelial growth factor-A expression, tumorigenicity, and chemosensitivity to curcumin in hepatocellular carcinoma [(Jia et al 2007)] ![] while the first panel succumbed to an attack of the clone tool and became Fig 2C of  siRNA-targeted COL8A1 inhibits proliferation, reduces invasion and enhances sensitivity to D-limonence treatment in hepatocarcinoma cells [(Zhao et al 2009)] . ![] , 
 At top: Fig 4  (E) The number of CFSEu00fe cells invasion to armpit lymph nodes in the absence or presence of Gas6 was measured by flow cytometry. With three frames, enlarged. Then Fig 4B from [Jia et al (2007a)] ; Fig 3B from [Jia et al (2007b)] ; and 6D from [Zhang et al (2015)] . ![file] It would be possible to bring Fig 3A of [Zhou et al (2012)] into the comparison as well, since the panels there appear to be permutations of 3B from Jia et al (2007b). ![] , 
 Below: Figure 2E again. Above: Figure 5 (A) from  siRNA targeted against matrix metalloproteinase 11 inhibits the metastatic capability of murine hepatocarcinoma cell Hca-F to lymph nodes [(Jia et al 2007)] .  Transwell migration assay was performed to measure Hca-F cells migration. Wright-Giemsa staining results of the lower surface filters showed that the cells migrated the filter (u00d7400). Overlaps marked. ![file] Note that the overlap is not completely: cells have been added to the 2010 version (or subtracted from the 2007 version), perhaps for aesthetic reasons. , 
 CORRIGENDUM 18 June 2019 When the article was first published there was an error in Figure 2C, 2D (panel 1, group of HcaF) and 2E (panel 1, group of HcaF). The raw data resulted in the publication of an incorrect figure. Despite the mistake, the conclusion remains the same. The correct figure is below: ![file] , 
 #5 Background [here] . ,