The century-old embryonal/gametogenesis hypothesis of tumors could link diverse tumors' malignant features together likely representing the real "stemness" of tumors. However, the genetic evidence to validate abnormal gametogenesis in tumors remains lacking. Here we show that p53 deficiency elicits abnormal gametogenesis from primordial germ cell-like stage to late oocyte-like stage and subsequent parthenogenetic activation. The similar upregulation of abnormal gametogenesis by p53 deficiency is observed both in p53(-/-) mouse model and cultured cancer cells. Notably, germ cell-like cells isolated from distinct tumors from p53(-/-) mice and cancer cell lines display potent tumorigenicity potential. Abnormal oogenesis induced by p53 deficiency and then spontaneous parthenogenetic activation endow tumors with imitated embryonic development, life cycle, and therapeutic resistance. Our study establishes the genetic evidence to support embryonal/gametogenesis theory of tumors and reveals a pivotal role of p53 in restricting abnormal gametogenesis that may represent a novel aspect for p53's tumor suppression.
[1]Fudan Univ, Huashan Hosp, Shanghai Med Coll, Dept Lab Med, Shanghai 200040, Peoples R China;
[2]Wake Forest Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA;
[3]Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA;
[4]China Med Univ, Grad Inst Basic Med Sci, Taichung 404, Taiwan;
[5]Asia Univ, Dept Biotechnol, Taichung 41354, Taiwan
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