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01-06-2012 | NON-THEMATIC REVIEW

The genetic/metabolic transformation concept of carcinogenesis

Authors: Leslie C. Costello, Renty B. Franklin

Published in: Cancer and Metastasis Reviews | Issue 1-2/2012

Abstract

The carcinogenesis process is poorly understood and subject to varying concepts and views. A rejuvenated interest has arisen regarding the role of altered cellular intermediary metabolism in the development and progression of cancer. As a result, differing views of the implications of altered metabolism in the development of cancer exist. None of the concepts recognize and incorporate the principles of cell metabolism to cell activity, which are applicable to all cells including the carcinogenesis process. This presentation incorporates a novel concept of carcinogenesis that includes a “genetic/metabolic” transformation that encompasses these principles of cell metabolism to cell activity. The intermediary metabolism transformation is essential to provide the bioenergetic/synthetic, growth/proliferation, and migration/invasive events of malignancy. The concept invokes an “oncogenetic transformation” for the development of neoplastic cells from their precursor normal cells; and a required “genetic/metabolic” transformation for facilitation of the development of the neoplastic cells to malignant cells with the manifestation of the malignant process. Such a concept reveals stages and events of carcinogenesis that provide approaches for the identification of biomarkers and for development of therapeutic agents. The presentation discusses the contemporary application of genetics and proteomics to altered cellular metabolism in cancer; and underscores the importance of proper integration of genetics and proteomics with biochemical and metabolic studies, and the consequences of inappropriate studies.

Vogelstein, B., & Kinzler, K. W. (2004). Cancer genes and the pathways they control. Nature Medicine, 10(8), 789–799.PubMedCrossRef

Costello, L. C., & Franklin, R. B. (2005). ‘Why do tumour cells glycolyse?’: from glycolysis through citrate to lipogenesis. Molecular and Cellular Biochemistry, 280(1–2), 1–8.PubMedCrossRef

Costello, L. C., & Franklin, R. B. (2006). The clinical relevance of the metabolism of prostate cancer; zinc and tumor suppression: connecting the dots. Molecular Cancer. doi:10.1186/1476-4598-5-17.

Costello, L. C., & Franklin, R. B. (2009). Integration of genetic, proteomic, and metabolic approaches in tumor cell metabolism. In K. Singh & L. C. Costello (Eds.), Mitochondria and cancer (pp. 79–92). New York: Springer.CrossRef

Costello, L. C., & Franklin, R. B. (2008). Transformations of malignant cells (an overview). In M. A. Hayat (Ed.), Methods of cancer diagnosis, therapy, and prognosis (pp. 3–16). New York: Springer.

Baggetto, L. G. (1992). Deviant energetic metabolism of glycolytic cancer cells. Biochimie, 74(11), 959–974.PubMedCrossRef

Kasper, S. (2008). Stem cells: the root of prostate cancer? Journal of Cell Physiology, 216(2), 332–336.CrossRef

Dang, C. V., & Samenza, G. L. (1999). Oncogenic alterations of metabolism. Trends in Biological Sciences, 24(2), 68–72.CrossRef

Hanahan, D., & Weinberg, R. A. (2000). The hallmarks of cancer. Cell, 100(1), 57–70.PubMedCrossRef

10.

Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell, 144(5), 646–674.PubMedCrossRef

11.

Alqawi, O., Wang, H. P., Espiritu, M., & Singh, G. (2007). Chronic hypoxia promotes an aggressive phenotype in rat prostate cancer cells. Free Radical Research, 41(7), 788–797.PubMedCrossRef

12.

Warburg, O., Wind, F., & Negelein, E. (1927). The metabolism of tumors in the body. Journal of General Physiology, 8(6), 519–530.PubMedCrossRef

13.

Moreadith, R. W., & Lehninger, A. L. (1984). The pathways of glutamate and glutamine oxidation by tumor cell mitochondria. Role of mitochondrial NAD(P) + −dependent malic enzyme. Journal of Biological Chemistry, 59(10), 6215–6221.

14.

Warburg, O. (1956). On the origin of cancer cells. Science, 123(3191), 309–314.PubMedCrossRef

15.

Weinhouse, S., Warburg, O., Burk, D., & Schade, A. L. (1956). On respiratory impairment in cancer cells. Science, 123(3191), 309–314.CrossRef

16.

Seyfried, T. N., & Shelton, L. M. (2010). Cancer as a metabolic disease. Nutrition and Metabolism. doi:10.1186/1743-7075-7-7.

17.

Huggins, C. (1946). The prostate secretion. Harvey Lectures, 42, 148–193.

18.

Costello, L. C., Guan, Z., Kukoyi, B., Feng, P., & Franklin, R. B. (2004). Terminal oxidation and the effects of zinc in prostate versus liver mitochondria. Mitochondrion, 4(4), 331–338.PubMedCrossRef

19.

Costello, L. C., Franklin, R. B., & Feng, P. (2005). Mitochondrial function, zinc, and intermediary metabolism relationships in normal prostate and prostate cancer. Mitochondrion, 5(3), 143–153.PubMedCrossRef

20.

Franklin, R. B., & Costello, L. C. (2007). Zinc as an anti-tumor agent in prostate cancer and in other cancers. Archives of Biochemistry and Biophysics, 463(2), 211–217.PubMedCrossRef

21.

Franklin, R. B., Feng, P., Milon, B. C., Desouki, M. M., Singh, K. K., Kajdacsy-Balla, A., et al. (2005). hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer. Molecular Cancer, 4(32), 13.

22.

Cortesi, M., Fridman, E., Volkov, A., Shilstein, S. S., Chechik, R., Breskin, A., Vartsky, D., Kleinman, N., Kogan, G., Moriel, E., Gladysh, V., Huszar, M., Ramon, J., Raviv, G., et al. (2008). Clinical assessment of the cancer diagnostic value of prostatic zinc: a comprehensive needle-biopsy study. Prostate, 68(9), 994–1006.PubMedCrossRef

23.

Johnson, L. A., Kanak, M. A., Kajdacsy-Balla, A., Pestaner, J. P., & Bagasra, O. (2010). Differential zinc accumulation and expression of human zinc transporter 1 (hZIP1) in prostate glands. Methods, 52(4), 316–321.PubMedCrossRef

24.

Cooper, J. E., & Farid, I. (1964). The role of citric acid in the physiology of the prostate: lactic/citrate ratios in benign and malignant prostatic homogenates as an index of prostatic malignancy. Journal of Urology, 92, 533–536.PubMed

25.

Costello, L. C., & Franklin, R. B. (2006). Tumor cell metabolism: the marriage of molecular genetics and proteomics with cellular intermediary metabolism; proceed with caution! Molecular Cancer. doi:10.1186/1476-4598-5-59.

26.

Costello, L. C. (2009). The effect of contemporary education and training of biomedical scientists on present and future medical research. Academic Medicine, 84(4), 459–463.PubMedCrossRef

27.

Singh, K. K., Desouki, M. M., Franklin, R. B., Costello, L. C. Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues. Molecular Cancer, doi: 10.1186/1476-4598-5-14.

28.

Costello, L. C., Littleton, G. K., & Franklin, R. B. (1978). Regulation of citrate-related metabolism in normal and neoplastic prostate. In R. K. Sharma & W. E. Criss (Eds.), Endocrine control in neoplasia (pp. 303–314). New York: Raven.

Title: The genetic/metabolic transformation concept of carcinogenesis
Authors: Leslie C. Costello
Renty B. Franklin
Publication date: 01-06-2012
Publisher: Springer US
Published in: Cancer and Metastasis Reviews / Issue 1-2/2012
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-011-9334-8

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