RETRACTED ARTICLE: Caveolin-1 promotes invasion and metastasis by upregulating Pofut1 expression in mouse hepatocellular carcinoma

Abstract

Caveolin-1 (Cav-1) is an important structural protein of caveolae and plays an oncogene-like role by influencing protein glycosylation in hepatocellular carcinoma (HCC) cells. However, the mechanism by which Cav-1 promotes invasion and metastasis capacity has not been completely clarified. In this study, we demonstrate that Pofut1 is a fucosyltransferase induced by Cav-1. Mouse Hepa1-6 HCC cells lacking Cav-1 expression exhibited low transcription levels of Pofut1 , whereas strong Pofut1 expression was found in high-metastasis-potential Hca-F cells with high levels of Cav-1. Cav-1 activated MAPK signaling and promoted phosphorylation of the transcription factors CREB, Sp1, HNF4A and c-Myc, which bound to the Pofut1 promoter region to induce its transcription. As Notch signaling receptors can be modified with O-fucose by Pofut1, we further showed that Cav-1-induced upregulation of Pofut1 expression activated the Notch pathway and thus enhanced invasion and metastasis by mouse HCC cells in vitro and in vivo. Collectively, our findings reveal a novel mechanism by which Cav-1 promotes tumor metastasis by upregulating expression of Pofut1, suggesting that Cav-1 may function as a new biomarker for HCC.

Caveolin‐1 increases glycolysis in pancreatic cancer cells and triggers cachectic states

“…Cav-1 increases the aggressiveness of cancer cells in pancreatic, hepatic, gastric, and prostate cancers. [28][29][30][31][32][33] However, cav-1 deficiency is seen as a driving force in squamous-cell carcinoma and breast cancer. 34,35 It appears that cav-1 exerts diversified effects in different cancers.…”

Functional Pro-metastatic Heterogeneity Revealed by Spiked-scRNAseq Is Shaped by Cancer Cell Interactions and Restricted by VSIG1

“…It is paradoxical that CC14 high-metastatic cells display high levels of specific vesicle trafficking markers, whereas these are notable in the lower metastatic cluster of CC36. Although CAV1, for instance, can have context-dependent functions (Sloan et al, 2004;Zhang et al, 2019, Campos et al, 2019, it is possible that instead of specific genes, it is the processes in which they participate, such as secretion, vesicle trafficking, and signaling, that mark pro-metastatic cells.…”

“…Of the most highly expressed genes in migrating cells, CAV1 was also strongly differentially expressed in highversus low-metastatic cells ( Figure 1F). We thus tested the role of this gene as a representative of the vesicular trafficking gene cohort: CAV1 knockdown (KD) (using a validated small hairpin RNA [shRNA]; Rausch et al, 2019) in E3 cells resulted in a reduction in transfilter migration by nearly 80% (Figure 3C), paralleling its involvement in other cases (Zhang et al, 2019, but see also Sloan et al, 2004).…”

The marine factor 3,5-dihydroxy-4-methoxybenzyl alcohol suppresses growth, migration and invasion and stimulates death of metastatic human prostate cancer cells: targeting diverse signaling processes

“…Culture of DHMBA was found to suppress migration and invasion of PC-3 or DU-145 cells in vitro . Furthermore, DHMBA diminished the levels of NF-κB p65, caveolin-1 and integrin β1, which are implicated in migration and invasion of cancer cells in vitro [36,37]. Decrease in these molecules may be important as the underlying mechanism by which DHMBA blocks migration and invasion of prostate cancer cells.…”