Low Levels of Sox2 are required for Melanoma Tumor-Repopulating Cell Dormancy

Theranostics
Qiong JiaHaibo Jia

Abstract

Tumorigenic cells, when facing a hostile environment, may enter a dormant state, leading to long-term tumor survival, relapse, and metastasis. To date, the molecular mechanism of tumor cell dormancy remains poorly understood. Methods: A soft, 3-dimentional (3D) fibrin gel culture system was used to mechanically select and grow highly malignant and tumorigenic melanoma tumor-repopulating cells (TRCs). We cultured control melanoma TRCs, TRCs with Sox2 knockdown, TRCs with Sox2 knockout, and a 2D control for in vitro and in vivo experiments. Western blotting, immunofluorescence, and flow cytometry analysis were performed to examine TRC dormancy and exit from dormancy. Results: Under a low-expression condition, we show that Sox2, a stemness molecule participates in dormancy regulation of highly tumorigenic cells that can repopulate a tumor (TRCs). Intriguingly, complete depletion of Sox2 via knockout results in dormancy exit and growth resumption of melanoma TRCs in culture and elevation of melanoma TRC apoptosis. Mice that are injected subcutaneously with Sox2-depleted melanoma TRCs do not form tumors and survive much longer than those injected with melanoma TRCs. We found that complete depletion of Sox2 promotes nuclear transloca...Continue Reading

Citations

Jun 13, 2020·Frontiers in Oncology·Angelica AvaglianoAlessandro Arcucci
Aug 23, 2019·Cancers·Rana Jahanban-EsfahlanPeyman Zare
Nov 17, 2020·Frontiers in Immunology·Antonella SistiguRuggero De Maria
Mar 9, 2021·Nature Cancer·Emma RissonJulio A Aguirre-Ghiso
Sep 3, 2020·Seminars in Cancer Biology·Sabah AkhtarHesham M Korashy
Apr 6, 2021·Frontiers in Oncology·Yunus AkkocDevrim Gozuacik

❮ Previous
Next ❯

Methods Mentioned

BETA
nuclear translocation
flow cytometry
immunoprecipitation
ChIP
gene
gene knockout

Software Mentioned

FlowJo
TIDE

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.