Nature sub-journal: Identify ways to limit metastatic cancer growth!

Cancer stem cells (CSCs) are key drivers behind the progression of malignant cancers with self-renewal, high metastases and resistance to therapy
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As cancer progresses, cancer cells exhibit phenotypic plasticity between stem-like and differentiated subpopulations, each of which can recreate the composition of the parental cells
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However, the mechanisms and functions of this plasticity remain largely unknown
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In a study "Cancer stem cell regulated phenotypic plasticity protects metastasized cancer cells from ferroptosis" published in Nature Communications, a research team led by Professor Zhu Tao from the Chinese University of Science and Technology of China (USTC), Chinese Academy of Sciences, uncovered the phenotypes regulated by CSCs The role of plasticity in metastatic colonization
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researchers designed an in vitro co-culture system and an in vivo co-implantation system
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Based on these systems, they discovered the ability of breast cancer stem cells (BCSCs) to suppress themselves through the BSCS-derived secretome
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Through screening, bioluminescence imaging and other means, they also found that DKK1 plays a pivotal role in the secretome
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DKK1 was identified as a key molecule that autonomously reduces the population of CSCs and subsequently promotes breast cancer metastatic colonization
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Further experiments showed that this autonomous restraint of BCSCs could prompt a large number of dormant disseminated tumor cells (DTCs) to exit from dormancy after reaching distant sites, and then achieve metastatic colonization
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However, small-molecule inhibitors of DKK1 can achieve almost complete blockade of lung metastasis in many models of BCSCs metastasis
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Ferroptosis is a non-apoptotic cell death process that results from metabolic abnormalities and lipid peroxidation
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Compared with primary breast cancer, lung metastatic cancer cells are subject to higher oxidative and iron stress
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The researchers revealed that highly aggressive CSCs have relatively high concentrations in lung metastases, and CSCs can secrete DKK1, which inhibits CSCs
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As CSCs are highly sensitive to ferroptosis, DKK1 secreted by CSCs protects cells in lung metastases from ferroptosis and thus metastatic growth
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The findings of this study shed light on the role of CSCs-regulated phenotypic plasticity in metastatic colonization and provide novel therapeutic approaches to effectively inhibit metastasis
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References:

https://medicalxpress.
com/news/2022-04-ways-limit-cancer-growth.
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