Apoptosis Reversal Promotes Cancer Stem Cell-Like Cell Formation.

Abstract:

:It has long been a puzzle in cancer treatment that despite the initial appearance of apoptosis, the process could be reversed in some cancer cells and often results in more aggressive tumors and metastasis. The mechanism for this recurrence is yet unknown. Here we report that human mammary carcinoma cells induced to undergo apoptosis could recover with increased tumorigenicity in vitro and in vivo, and induced lymph node metastasis. Specifically, the reversed cells underwent epithelial-to-mesenchymal transitions in the primary tumors in situ, and mesenchymal-to-epithelial transitions in the metastatic cells. Flow cytometry confirmed an elevated percentage of cells carrying cancer stem cells (CSCs) markers (CD44+/CD24-) in the reversed breast cancer cell population, with hypomethylated CD44 promoters and hypermethylated CD24 promoters. More importantly, CSCs were generated anew from non-stem cancer cells after apoptosis reversal possibly through epigenetic modifications. The results from this study can open doors to discovering more effective cancer treatments by suppressing apoptosis reversal.

journal_name

Neoplasia

authors

Xu Y,So C,Lam HM,Fung MC,Tsang SY

doi

10.1016/j.neo.2018.01.005

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

295-303

issue

3

eissn

1522-8002

issn

1476-5586

pii

S1476-5586(17)30395-0

journal_volume

20

pub_type

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