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Cancer Cells Arise From Bacteria

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Cancer Cells Arise From Bacteria

Qing-Lin Dong et al. Cancer Cell Int.

Abstract

Background: The origin of cancer cells is the most fundamental yet unresolved problem in cancer research. Cancer cells are thought to be transformed from the normal cells. However, recent studies reveal that the primary cancer cells (PCCs) for cancer initiation and secondary cancer cells (SCCs) for cancer progression are formed in but not transformed from the senescent normal and cancer cells, respectively. Nevertheless, the cellular mechanism of PCCs/SCCs formation is unclear. Here, based on the evidences (1) the nascent PCCs/SCCs are small and organelle-less resembling bacteria; (2) our finding that the cyanobacterium TDX16 acquires its algal host DNA and turns into a new alga TDX16-DE by de novo organelle biogenesis, and (3) PCCs/SCCs formations share striking similarities with TDX16 development and transition, we propose the bacterial origin of cancer cells (BOCC).

Presentation of the hypothesis: The intracellular bacteria take up the DNAs of the senescent/necrotic normal cells/PCCs and then develop into PCCs/SCCs by hybridizing the acquired DNAs with their own ones and expressing the hybrid genomes.

Testing the hypothesis: BOCC can be confirmed by testing BOCC-based predictions, such as normal cells with no intracellular bacteria can not "transform" into cancer cells in any conditions.

Implications of the hypothesis: According to BOCC theory: (1) cancer cells are new single-celled eukaryotes, which is why the hallmarks of cancer are mostly the characteristics of protists; (2) genetic changes and instabilities are not the causes, but the consequences of cancer cell formation; and (3) the common role of carcinogens, infectious agents and relating factors is inducing or related to cellular senescence rather than mutations. Therefore, BOCC theory provides new rationale and direction for cancer research, prevention and therapy.

Keywords: Bacteria; Cancer cells; Cellular senescence; DNA acquisition; Hybridization; Organelle biogenesis; Origin.

Figures

Fig. 1
Fig. 1
Release of TDX16 from the senescent H. pluvialis cell. A An enlarged senescent H. pluvialis cell. B A massive blue spheroid (top right) with compacted TDX16 cells was released from the ruptured senescent H. pluvialis cell
Fig. 2
Fig. 2
TDX16 development and transition into TDX16-DE. A Very small TDX16 cells with electron-dense HGBs multiplied by asymmetric division in the senescent H. pluvialis cell, scale bar 5 μm. B Small DTX16 cells filled up the cellular space of a senescent H. pluvialis cell, scale bar 0.5 μm. C Five TDX16 cells within a sporangium, scale bar 1 μm. D A TDX16-DE cell contains a large “e-shaped” chloroplast (C) with an embedded pyrenoid (P), a nucleus (N), a mitochondrion (M) and two vacuoles (V), scale bar 0.5 μm
Fig. 3
Fig. 3
Cartoon illustrating the formation of cancer cells. a The normal cell/PCC undergoes senescence and bloats into a PGC/PGCC with a large nucleus (N). leading to the activation of the dormant intracellular bacterium (B) and the invasion of the extracellular bacterium. b The bacterium intrudes into the large PGC/PGCC nucleus, takes up the nuclear DNA and retains the obtained DNA in DSB, and thus turns into the small nascent cancer cell (NC): PCC/SCC. c NC multiplies in the nucleus by asymmetric division, some of which penetrate the nuclear envelope (NE) into the cytoplasm. d All NCs enter cytoplasm after the rupture of NE, and continue to proliferate. During this process, some NCs protrude and escape from the necrotic PGCs/PGCCs; while most NCs aggregate into a spheroid. e A spheroid consist of NCs is liberated from the ruptured PGCs/PGCCs. f As NC increases in size, DSB disrupts and thus the acquired eukaryotic DNA and the bacterial one fragments and hybridizes into a hybrid genome; concurrently, a peripheral double membrane segment (DMS) is synthesized by fusion of the cytoplasmic membrane-derived vesicles. g NC further enlarges, DMS extends into a closed double membrane (DM), enclosing the total cytoplasm, and thus gives rise to a single multifunctional organelle (MO). Inside MO, a mitochondrion (M) is assembled by encapsulating the selected relevant components (e.g., DNA) with the double membrane synthesized by fusion of the inner DM membrane-derived vesicles; meanwhile, a small opening (O) is formed on DM allowing the selective release of MO matrix. h The released MO matrix builds up the eukaryotic cytoplasm (EC), and the newly assembled mitochondrion detaches from MO into EC; while new mitochondria continue to develop in MO, resulting the diminishment of MO. i After all mitochondria enter EC, MO dwindles into a nucleus (N), such that NC develops into a large mature PCC/SCC

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