Cancer Cell De-Differentiation: Plasticity-Driven Stratagem For Tumor Metastasis and Recurrence

Overview

Journal Curr Stem Cell Res Ther

Publisher Bentham Science Publishers

Specialties Cell Biology
Pharmacology

Date 2022 Jun 9

PMID 35676837

Authors

Sanaa El Marsafy

Jerome Larghero

Affiliations

Soon will be listed here.

Abstract

Tumor recurrence is a colossal challenge in clinical oncology. This multifactorial problem is attributed to the emergence of additional genetic mutations and the presence of dormant cancer cells. However, the plasticity of non-stem cancer cells and the acquisition of cancer stem cell (CSC) functionality is another contributing factor to tumor recurrence. Herein, I focus attention on the mechanisms that fuel cancer cell de-differentiation and the interplay between intra-cellular regulators and tumor microenvironment (TME) landscape that promotes cancer cell stemness. Our understanding of the mechanisms underlying tumor cell de-differentiation is crucial for developing innovative therapeutic strategies that prevent cancer from ever recurring.

Citing Articles

Deciphering the Role of Cancer Stem Cells: Drivers of Tumor Evolution, Therapeutic Resistance, and Precision Medicine Strategies.

El-Tanani M, Rabbani S, Satyam S, Rangraze I, Wali A, El-Tanani Y Cancers (Basel). 2025; 17(3).

PMID: 39941751 PMC: 11815874. DOI: 10.3390/cancers17030382.

References

Bachoo R, Maher E, Ligon K, Sharpless N, Chan S, You M . Epidermal growth factor receptor and Ink4a/Arf: convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis. Cancer Cell. 2002; 1(3):269-77. DOI: 10.1016/s1535-6108(02)00046-6. View

Clara J, Monge C, Yang Y, Takebe N . Targeting signalling pathways and the immune microenvironment of cancer stem cells - a clinical update. Nat Rev Clin Oncol. 2019; 17(4):204-232. DOI: 10.1038/s41571-019-0293-2. View

Schwitalla S, Fingerle A, Cammareri P, Nebelsiek T, Goktuna S, Ziegler P . Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell. 2013; 152(1-2):25-38. DOI: 10.1016/j.cell.2012.12.012. View

Barker N, Ridgway R, van Es J, van de Wetering M, Begthel H, van den Born M . Crypt stem cells as the cells-of-origin of intestinal cancer. Nature. 2008; 457(7229):608-11. DOI: 10.1038/nature07602. View

Gomatou G, Syrigos N, Vathiotis I, Kotteas E . Tumor Dormancy: Implications for Invasion and Metastasis. Int J Mol Sci. 2021; 22(9). PMC: 8124645. DOI: 10.3390/ijms22094862. View

Hen O, Barkan D . Dormant disseminated tumor cells and cancer stem/progenitor-like cells: Similarities and opportunities. Semin Cancer Biol. 2019; 60:157-165. DOI: 10.1016/j.semcancer.2019.09.002. View

Talukdar S, Bhoopathi P, Emdad L, Das S, Sarkar D, Fisher P . Dormancy and cancer stem cells: An enigma for cancer therapeutic targeting. Adv Cancer Res. 2019; 141:43-84. DOI: 10.1016/bs.acr.2018.12.002. View

Pienta K, Hammarlund E, Brown J, Amend S, Axelrod R . Cancer recurrence and lethality are enabled by enhanced survival and reversible cell cycle arrest of polyaneuploid cells. Proc Natl Acad Sci U S A. 2021; 118(7). PMC: 7896294. DOI: 10.1073/pnas.2020838118. View

Boumahdi S, de Sauvage F . The great escape: tumour cell plasticity in resistance to targeted therapy. Nat Rev Drug Discov. 2019; 19(1):39-56. DOI: 10.1038/s41573-019-0044-1. View

10.

Gupta P, Pastushenko I, Skibinski A, Blanpain C, Kuperwasser C . Phenotypic Plasticity: Driver of Cancer Initiation, Progression, and Therapy Resistance. Cell Stem Cell. 2018; 24(1):65-78. PMC: 7297507. DOI: 10.1016/j.stem.2018.11.011. View

11.

Wang W, Groenendyk J, Michalak M . Endoplasmic reticulum stress associated responses in cancer. Biochim Biophys Acta. 2014; 1843(10):2143-9. DOI: 10.1016/j.bbamcr.2014.01.012. View

12.

Munoz P, Iliou M, Esteller M . Epigenetic alterations involved in cancer stem cell reprogramming. Mol Oncol. 2012; 6(6):620-36. PMC: 5528346. DOI: 10.1016/j.molonc.2012.10.006. View

13.

Saggese P, Sellitto A, Martinez C, Giurato G, Nassa G, Rizzo F . Metabolic Regulation of Epigenetic Modifications and Cell Differentiation in Cancer. Cancers (Basel). 2020; 12(12). PMC: 7765496. DOI: 10.3390/cancers12123788. View

14.

Das P, Pillai S, Rakib M, Khanam J, Gopalan V, Lam A . Plasticity of Cancer Stem Cell: Origin and Role in Disease Progression and Therapy Resistance. Stem Cell Rev Rep. 2020; 16(2):397-412. DOI: 10.1007/s12015-019-09942-y. View

15.

Friedmann-Morvinski D, Verma I . Dedifferentiation and reprogramming: origins of cancer stem cells. EMBO Rep. 2014; 15(3):244-53. PMC: 3989690. DOI: 10.1002/embr.201338254. View

16.

Mittal P, Roberts C . The SWI/SNF complex in cancer - biology, biomarkers and therapy. Nat Rev Clin Oncol. 2020; 17(7):435-448. PMC: 8723792. DOI: 10.1038/s41571-020-0357-3. View

17.

Jahangiri L, Tsaprouni L, Trigg R, Williams J, Gkoutos G, Turner S . Core regulatory circuitries in defining cancer cell identity across the malignant spectrum. Open Biol. 2020; 10(7):200121. PMC: 7574545. DOI: 10.1098/rsob.200121. View

18.

Chen X, Yang F, Zhang T, Wang W, Xi W, Li Y . MiR-9 promotes tumorigenesis and angiogenesis and is activated by MYC and OCT4 in human glioma. J Exp Clin Cancer Res. 2019; 38(1):99. PMC: 6385476. DOI: 10.1186/s13046-019-1078-2. View

19.

Murakami S, Ninomiya W, Sakamoto E, Shibata T, Akiyama H, Tashiro F . SRY and OCT4 Are Required for the Acquisition of Cancer Stem Cell-Like Properties and Are Potential Differentiation Therapy Targets. Stem Cells. 2015; 33(9):2652-63. DOI: 10.1002/stem.2059. View

20.

Novak D, Huser L, Elton J, Umansky V, Altevogt P, Utikal J . SOX2 in development and cancer biology. Semin Cancer Biol. 2019; 67(Pt 1):74-82. DOI: 10.1016/j.semcancer.2019.08.007. View