title: The paradigm of mutant p53-expressing cancer stem cells and drug resistance.
abstract: It is well accepted that expression of mutant p53 involves the gain of oncogenic-specific activities accentuating the malignant phenotype. Depending on the specific cancer type, mutant p53 can contribute to either the early or the late events of the multiphase process underlying the transformation of a normal cell into a cancerous one. This multifactorial system is evident in ~50% of human cancers. Mutant p53 was shown to interfere with a variety of cellular functions that lead to augmented cell survival, cellular plasticity, aberration of DNA repair machinery and other effects. All these effects culminate in the acquisition of drug resistance often seen in cancer cells. Interestingly, drug resistance has also been suggested to be associated with cancer stem cells (CSCs), which reside within growing tumors. The notion that p53 plays a regulatory role in the life of stem cells, coupled with the observations that p53 mutations may contribute to the evolvement of CSCs makes it challenging to speculate that drug resistance and cancer recurrence are mediated by CSCs expressing mutant p53.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Shetzer
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Hilla
authors.initials: H
authors.lastname: Solomon
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Koifman
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Alina
authors.initials: A
authors.lastname: Molchadsky
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Stav
authors.initials: S
authors.lastname: Horesh
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel varda.rotter@weizmann.ac.il.
authors.forename: Varda
authors.initials: V
authors.lastname: Rotter
mesh_terms: D000818:Animals; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability; D006801:Humans; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53