Apoptosis Reversal Promotes Cancer Stem Cell-Like Cell Formation

Neoplasia : an International Journal for Oncology Research
Yiyue XuSuk-Ying Tsang

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.

Citations

May 31, 2019·Cellular Oncology (Dordrecht)·Mahendra SeerviT R SanthoshKumar
Feb 28, 2020·Experimental and Therapeutic Medicine·Huan YangNong Cao
Mar 7, 2019·Royal Society Open Science·Ho Man Tang, Ho Lam Tang
Feb 6, 2020·Cancer Metastasis Reviews·Souneek ChakrabortyAnindya Goswami
Nov 6, 2018·International Journal of Molecular Sciences·Mohamed A EldeebMohamed A Ragheb
Jun 13, 2019·Biology Open·Ho Man Tang, Ho Lam Tang
Nov 13, 2020·The FEBS Journal·Camila Castillo FerrerGabriel Ichim
Jun 11, 2020·Cell Reports·Kevin BerthenetGabriel Ichim
Jan 23, 2021·Cancers·Vanessa CastelliMichele d'Angelo
Nov 18, 2020·Biochemistry. Biokhimii︠a︡·I I ZakharovG E Onishchenko
Dec 3, 2020·International Journal of Molecular Sciences·Razmik Mirzayans, David Murray
Aug 8, 2021·Cancers·Victoria ZaitcevaBoris Zhivotovsky

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Methods Mentioned

BETA
Fluorescence-Activated Cell Sorting
xenograft
Flow Cytometric
Magnetic-Activated
FACS
PCR
xenografts
flow cytometry

Software Mentioned

FACSuite
FV1000

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