In Cancer Cell this week, a team led by researchers at MD Anderson Cancer Center report that p53-mediated senescence in breast cancer cells impairs the apoptotic response to chemotherapy. The team shows that mammary tumors with mutant p53 exhibit a "superior clinical response" compared to tumors with wild-type p53 — p53 mutant tumors treated with doxorubicin continued to proliferate, leading to abnormal mitosis, whereas wild-type p53 tumors arrested when treated with doxorubicin. "Senescent tumor cells persisted, secreting senescence-associated cytokines exhibiting autocrine/paracrine activity and mitogenic potential," the authors write. "Wild-type p53 activity hinders chemotherapy response."
Also in Cancer Cell this week, researchers in Canada and Ireland report that ID1 and ID3 work together to regulate the self-renewal capacity of human colon cancer-initiating cells. ID1 and ID3 function together in this capacity through cell-cycle restriction driven p21, a cell-cycle inhibitor, the authors write. The regulation of p21 by ID1 and ID3 is central to preventing the accumulation of DNA damage to cancer-initiating cells and keeping them functional. "Additionally, silencing of ID1 and ID3 increases sensitivity of cancer-initiating cells to the chemotherapeutic agent oxaliplatin, linking tumor initiation function with chemotherapy resistance," they add.
Rockefeller University's Teresa Davoli and Titia de Lange report that tetraploidization in cells is driven by telomere dysfunction and promotes tumorigenesis in mouse cells. Endoreduplication and mitotic failure occur in human fibroblasts and mammary epithelial cells during telomere crisis, and telomere-driven tetraploidization can lead to the transformation of mouse cells into cancer cells, the authors write. "Similar to human solid cancers, the resulting tumors evolved subtetraploid karyotypes," they add. "These data establish that telomere-driven tetraploidization is induced by critically short telomeres and has the potential to promote tumorigenesis in early cancerous lesions."