The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Association of Autophagy Defect with a Malignant Phenotype and Poor Prognosis of Hepatocellular Carcinoma
Abstract
Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis. The role of autophagy and the prognostic value of autophagic genes are largely unknown in HCC. Here, we showed decreased expression of autophagic genes and their corresponding autophagic activity and increased expression of the antiapoptotic gene Bcl-xL in HCC cell lines compared with a normal hepatic cell line. We also found decreased expression of the autophagic gene Beclin 1 in 44 HCC tissue samples compared with adjacent nontumor tissues. In addition, we found that the most aggressive malignant HCC cell lines and HCC tissues with recurrent disease displayed much lower autophagic levels, especially when Bcl-xL was overexpressed. Interestingly, in a tissue microarray study consisting of 300 HCC patients who underwent curative resection, the expression of Beclin 1 was only significantly correlated with disease-free survival (DFS; P < 0.0001) and overall survival (OS; P < 0.0001) in the Bcl-xL+ group. Multivariate and univariate analyses also revealed that Beclin 1 expression was an independent predictor for DFS and OS in Bcl-xL+ patients. In addition, we found a significant correlation between Beclin 1 expression and tumor differentiation in Bcl-xL+ but not in Bcl-xL− HCC patients. In conclusion, our data showed expression of autophagic genes and their corresponding autophagic activities were suppressed in HCC. The autophagy defects synergized with altered apoptotic activity might facilitate tumor malignant differentiation, which results in a more aggressive cancer cell phenotype and poor prognosis of HCC. [Cancer Res 2008;68(22):9167–75]
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Citations
Cites
Autophagy fights disease through cellular self-digestion
Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008) · Nature · doi:10.1038/nature06639 · Cited by 6,452
Induction of autophagy and inhibition of tumorigenesis by beclin 1
Liang, X. H., Jackson, S., Seaman, M., Brown, K., Kempkes, B., Hibshoosh, H., & Levine, B. (1999) · Nature · doi:10.1038/45257 · Cited by 3,347
Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
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Yue, Z., Jin, S., Yang, C., Levine, A. J., & Heintz, N. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2436255100 · Cited by 2,116
Mathew, R., Karantza-Wadsworth, V., & White, E. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2254 · Cited by 1,798
Growth factor regulation of autophagy and cell survival in the absence of apoptosis
Lum, J. J., Bauer, D. E., Kong, M., Harris, M. H., Li, C., Lindsten, T., & Thompson, C. B. (2005) · Cell · doi:10.1016/j.cell.2004.11.046 · Cited by 1,487
Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes
Shimizu, S., Kanaseki, T., Mizushima, N., Mizuta, T., Arakawa-Kobayashi, S., Thompson, C. B., & Tsujimoto, Y. (2004) · Nature Cell Biology · doi:10.1038/ncb1192 · Cited by 1,358
Cited by
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894
Self-citationGuidelines for the use and interpretation of assays for monitoring autophagy
Klionsky, D. J., Abdalla, F. C., Abeliovich, H., Abraham, R. T., Acevedo-Arozena, A., Adeli, K., Agholme, L., Agnello, M., Agostinis, P., Aguirre-Ghiso, J. A., et al. (2012) · Autophagy · doi:10.4161/auto.19496 · Cited by 3,996
Self-citationGuidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,897
Self-citationAutophagy in chronic liver diseases: the two faces of Janus
Gual, P., Gilgenkrantz, H., & Lotersztajn, S. (2017) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00295.2016 · Cited by 91
Jia, Y.-L., Xu, M., Dou, C.-W., Liu, Z.-K., Xue, Y.-M., Yao, B.-W., Ding, L.-L., Tu, K.-S., Zheng, X., & Liu, Q.-G. (2016) · Cell Death & Disease · doi:10.1038/cddis.2016.247 · Cited by 50
Autophagy and senescence: the molecular mechanisms and implications in liver diseases
Li, Q., Lin, Y., Liang, G., Xiao, N., Zhang, H., Yang, X., Yang, J., & Liu, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242316880 · Cited by 43
Osman, N. A. A., Abd El-Rehim, D. M., & Kamal, I. M. (2015) · Tumor Biology · doi:10.1007/s13277-015-3068-0 · Cited by 37
Metadata
- Authors
- Ding, Z.-B., Shi, Y.-H., Zhou, J., Qiu, S.-J., Xu, Y., Dai, Z., Shi, G.-M., Wang, X.-Y., Ke, A.-W., Wu, B., & Fan, J.
- Venue
- Cancer Research
- Published
- 2008-11-14
- Volume
- 68
- Issue
- 22
- Pages
- 9167-9175
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2096661568
- Cited by
- 273
- References
- 7
- FWCI
- 7.88
- Type
- journal article
- Language
- en
- Open access
- closed
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