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Cancer as a mitochondrial metabolic disease.

Seyfried TN - Front Cell Dev Biol (2015)

Bottom Line: Cancer is widely considered a genetic disease involving nuclear mutations in oncogenes and tumor suppressor genes.This view persists despite the numerous inconsistencies associated with the somatic mutation theory.The evidence from these experiments is difficult to reconcile with the somatic mutation theory, but is consistent with the notion that cancer is primarily a mitochondrial metabolic disease.

View Article: PubMed Central - PubMed

Affiliation: Biology Department, Boston College Chestnut Hill, MA, USA.

ABSTRACT
Cancer is widely considered a genetic disease involving nuclear mutations in oncogenes and tumor suppressor genes. This view persists despite the numerous inconsistencies associated with the somatic mutation theory. In contrast to the somatic mutation theory, emerging evidence suggests that cancer is a mitochondrial metabolic disease, according to the original theory of Otto Warburg. The findings are reviewed from nuclear cytoplasm transfer experiments that relate to the origin of cancer. The evidence from these experiments is difficult to reconcile with the somatic mutation theory, but is consistent with the notion that cancer is primarily a mitochondrial metabolic disease.

No MeSH data available.


Related in: MedlinePlus

Mouse embryo cloned from tumor cell nucleus. An E-9.5 mouse embryo cloned from a melanoma-derived R545-1 embryonic stem cell. The embryo expressed neural tube closure, a beating heart, and normal limb bud development consistent with regulated cell growth. The result shows that the nucleus of a malignant melanoma can direct early mouse development when placed into normal cytoplasm containing normal mitochondria. However, irreversible genetic alterations, from the melanoma donor genome, disrupted complete development similar to the situation found in Lucke frogs that were cloned from nuclei of renal tumors (McKinnell et al., 1969). Reprinted from in this figure (Hochedlinger et al., 2004) with permission.
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Figure 2: Mouse embryo cloned from tumor cell nucleus. An E-9.5 mouse embryo cloned from a melanoma-derived R545-1 embryonic stem cell. The embryo expressed neural tube closure, a beating heart, and normal limb bud development consistent with regulated cell growth. The result shows that the nucleus of a malignant melanoma can direct early mouse development when placed into normal cytoplasm containing normal mitochondria. However, irreversible genetic alterations, from the melanoma donor genome, disrupted complete development similar to the situation found in Lucke frogs that were cloned from nuclei of renal tumors (McKinnell et al., 1969). Reprinted from in this figure (Hochedlinger et al., 2004) with permission.

Mentions: The work of Hochedlinger, Jaenisch, and colleagues also supported the findings from the Lucke frog and the mouse medulloblastoma experiments (Hochedlinger et al., 2004). These investigators found that the nuclei of mouse melanoma cells could produce normal-appearing blastocysts without signs of dysregulated cell proliferation. They also showed that normal blastocysts could be formed from p53 -/- breast cancer cells, and that normal blastocysts and embryonic cell lines could be formed from melanoma nuclei. Figure 2 shows an image from their study of mouse embryo cloned from the nucleus of a melanoma. These investigators suggested that the oocyte environment could suppress the malignant phenotype of the various tumor types, and that tumor nuclei could direct normal appearing development in early mouse embryos (Hochedlinger et al., 2004; Seyfried, 2012d). The oocyte cytoplasm would be expected to contain normal mitochondria. Based on the previously mentioned studies in cybrids, frogs, and mice, it would be reasonable to assume that the respiratory competent normal mitochondria would suppress tumorigenicity. It can be suggested that tumor nuclei would direct normal development as long as normal functioning mitochondria exist in the cytoplasm. However, the authors showed that tumors could form in some mice cloned from tumor nuclei, as long as the Ras oncogene was expressed together with the tumor-associated mutations. It is now known that the Ras oncogene induces tumorigenesis through an inhibitory effect on mitochondrial oxidative phosphorylation (Hu et al., 2012). Hence, respiratory damage is an essential requirement for tumorigenesis.


Cancer as a mitochondrial metabolic disease.

Seyfried TN - Front Cell Dev Biol (2015)

Mouse embryo cloned from tumor cell nucleus. An E-9.5 mouse embryo cloned from a melanoma-derived R545-1 embryonic stem cell. The embryo expressed neural tube closure, a beating heart, and normal limb bud development consistent with regulated cell growth. The result shows that the nucleus of a malignant melanoma can direct early mouse development when placed into normal cytoplasm containing normal mitochondria. However, irreversible genetic alterations, from the melanoma donor genome, disrupted complete development similar to the situation found in Lucke frogs that were cloned from nuclei of renal tumors (McKinnell et al., 1969). Reprinted from in this figure (Hochedlinger et al., 2004) with permission.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493566&req=5

Figure 2: Mouse embryo cloned from tumor cell nucleus. An E-9.5 mouse embryo cloned from a melanoma-derived R545-1 embryonic stem cell. The embryo expressed neural tube closure, a beating heart, and normal limb bud development consistent with regulated cell growth. The result shows that the nucleus of a malignant melanoma can direct early mouse development when placed into normal cytoplasm containing normal mitochondria. However, irreversible genetic alterations, from the melanoma donor genome, disrupted complete development similar to the situation found in Lucke frogs that were cloned from nuclei of renal tumors (McKinnell et al., 1969). Reprinted from in this figure (Hochedlinger et al., 2004) with permission.
Mentions: The work of Hochedlinger, Jaenisch, and colleagues also supported the findings from the Lucke frog and the mouse medulloblastoma experiments (Hochedlinger et al., 2004). These investigators found that the nuclei of mouse melanoma cells could produce normal-appearing blastocysts without signs of dysregulated cell proliferation. They also showed that normal blastocysts could be formed from p53 -/- breast cancer cells, and that normal blastocysts and embryonic cell lines could be formed from melanoma nuclei. Figure 2 shows an image from their study of mouse embryo cloned from the nucleus of a melanoma. These investigators suggested that the oocyte environment could suppress the malignant phenotype of the various tumor types, and that tumor nuclei could direct normal appearing development in early mouse embryos (Hochedlinger et al., 2004; Seyfried, 2012d). The oocyte cytoplasm would be expected to contain normal mitochondria. Based on the previously mentioned studies in cybrids, frogs, and mice, it would be reasonable to assume that the respiratory competent normal mitochondria would suppress tumorigenicity. It can be suggested that tumor nuclei would direct normal development as long as normal functioning mitochondria exist in the cytoplasm. However, the authors showed that tumors could form in some mice cloned from tumor nuclei, as long as the Ras oncogene was expressed together with the tumor-associated mutations. It is now known that the Ras oncogene induces tumorigenesis through an inhibitory effect on mitochondrial oxidative phosphorylation (Hu et al., 2012). Hence, respiratory damage is an essential requirement for tumorigenesis.

Bottom Line: Cancer is widely considered a genetic disease involving nuclear mutations in oncogenes and tumor suppressor genes.This view persists despite the numerous inconsistencies associated with the somatic mutation theory.The evidence from these experiments is difficult to reconcile with the somatic mutation theory, but is consistent with the notion that cancer is primarily a mitochondrial metabolic disease.

View Article: PubMed Central - PubMed

Affiliation: Biology Department, Boston College Chestnut Hill, MA, USA.

ABSTRACT
Cancer is widely considered a genetic disease involving nuclear mutations in oncogenes and tumor suppressor genes. This view persists despite the numerous inconsistencies associated with the somatic mutation theory. In contrast to the somatic mutation theory, emerging evidence suggests that cancer is a mitochondrial metabolic disease, according to the original theory of Otto Warburg. The findings are reviewed from nuclear cytoplasm transfer experiments that relate to the origin of cancer. The evidence from these experiments is difficult to reconcile with the somatic mutation theory, but is consistent with the notion that cancer is primarily a mitochondrial metabolic disease.

No MeSH data available.


Related in: MedlinePlus