The reproductive life cycle of cancer: Hypotheses of cell of origin, TP53 drivers and stem cell conversions in the light of the atavistic cancer cell theory
Autor: | Vladimir F. Niculescu |
---|---|
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Cell type Carcinogenesis Somatic cell Biology Epigenesis Genetic 03 medical and health sciences 0302 clinical medicine Cancer stem cell Cell Line Tumor Neoplasms medicine Asymmetric cell division Humans Neoplasm Metastasis Mitosis Cancer Cell Differentiation General Medicine Models Theoretical Genes p53 medicine.disease Cell biology Gene Expression Regulation Neoplastic 030104 developmental biology Cancer cell Neoplastic Stem Cells Tumor Suppressor Protein p53 Stem cell 030217 neurology & neurosurgery DNA Damage |
Zdroj: | Medical Hypotheses. 123:19-23 |
ISSN: | 0306-9877 |
DOI: | 10.1016/j.mehy.2018.12.006 |
Popis: | Polyploid giant cancer cells (PGCCs) found in different solid cancers are reproductive cyst-like structures surrounded by an actin envelop. They give rise by hyper-polyploidisation to numerous progeny (microcells, neotic cells) that start a primitive multi-lined lineage and generate subsequent PGCCs by asymmetric cell division and cyclic differentiation. This cancer cell life cycle has multiple similarities with the life cycle of lower eukaryotes (protists) substantiating the atavistic theory of cancer. The primitive cancer life cycle contains several cell types including primary cancer stem cells, somatic cells, as well as reproductive cells, that differentiate new atavistic cyst like structures (aCLSs, PGCCs). Accordingly, cancer stem cells are not transformed normal stem cells (hSCs). Similarities between CSCs and normal hSCs arise from the evolutionary common origin of primitive eukaryotes and more highly evolved eukaryotic cells (stemness evolution). The cell of origin of cancer, as postulated here is a deregulated human cell that has lost, not only relevant control mechanisms and mitotic capacity, but also its normal human p53 network becoming useless for the atavistic life cycle. We believe that this protoprecursor of cancer reactivates an ancient primitive TP53 network originating from the common eukaryotic ancestor. This atavistic p53 helpes to repair genotoxic DNA damages of reproductive cancer cells including CSCs but not DNA damages of somatic cancer cells exposed to genotoxic stress. |
Databáze: | OpenAIRE |
Externí odkaz: |