Our current findings provide molecular genetic evidence that Cav-1 plays an important role in regulating glycosyltransferase expression and may participate in the abnormal glycosylation that mediates the invasion and metastasis of HCC.
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.
A cDNA microarray analysis followed by verification experiments identified that caveolin-1 (CAV1), a growth-promoting protein in HCC, was markedly decreased upon ADI1 overexpression.
POH1 contributes to hyperactivation of TGF-β signaling and facilitates hepatocellular carcinoma metastasis through deubiquitinating TGF-β receptors and caveolin-1.
<b>Conclusions:</b> In summary, CAV-1 protein overexpression is at risk for liver cirrhosis and HCC derived from cirrhosis, and CAV-1 is also a promising prognostic predictor in HCC.
Further studies of the function and relationship between CAV-1 or HK2 expression are warranted to explore the potential of these proteins as metabolic targets for the treatment of HCC.
The overexpression of Cav-1 in Hep3B promoted the cell invasion, whereas its knockdown in SK-Hep1 suppressed the invasive feature, which confirms that the overexpression of Cav-1 is closely associated with cell invasion of liver carcinoma.
MIM-B combined with caveolin-1 promotes metastasis of HCC, and elevated MIM-B and caveolin-1 expression levels are associated with a poor prognosis in HCC patients; therefore, MIM-B and caveolin-1 may represent novel targets for the diagnosis and treatment of HCC.
Moreover, the linkage disequilibrium of CAV1 polymorphisms was analyzed by Haploview.The AG genotype and A allele of rs1049334 showed significantly higher frequency in HCC patients than that of chronic HBV patients and the healthy controls (P < .05); so their carriage obviously increased the susceptibility to HBV-related HCC, irrespective of the fact whether individuals were infected with hepatitis B virus or not (AG vs GG: OR 1.958, 95% CI 1.050-3.650, OR 1.899, 95% CI 1.034-3.487; A vs G: OR 1.667, 95% CI 1.033-2.689, OR 1.777, 95% CI 1.103-2.863).
In conclusion reciprocal activating crosstalk between c-Met and CAV1 promoted oncogenic signaling of c-Met contributed to the initiation and progression of HCC.
We found that CAV1rs729949 was statistically associated with increased risk of HCC (odds ratio (OR) = 1.28; 95% confidence interval (CI), 1.11-1.48; P = 8.53 × 10(-4)), even after Bonferroni correction (P = 5.97 × 10(-3)); the expression levels of CAV1 in cancer tissues were significantly lower than those in adjacent normal tissues (P = 0.012).
There were significant differences between the HCC and control groups in the distributions of the CAV-1G14713A genotypes (p=0.0124), and these carrying AG and AA genotypes had a higher risk for HCC, compared with those with the GG genotype (odds ratio=1.51 and 1.94, respectively).
In the literature, it has been reported that single nucleotide variation of caveolin-1 gene (CAV1) plays an important role in risk of several types of cancer, such as hepatoma, leukemia, nasopharyngeal carcinoma, oral, breast, bladder and prostate cancer, but we are not aware of any reports on upper urothelial tract cancer.
Our results suggested that differential levels of P-gp, Cav-1 and FASN play a major role in acquired resistant phenotype whereas FASN level was associated with the presentation of inherent resistant phenotype in HCC.