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Lineage Plasticity in Cancer: The Tale of a Skin-Walker

Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Kerala 695014, India
Manipal Academy of Higher Education (MAHE), Manipal 576104, India
Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India
Authors to whom correspondence should be addressed.
Academic Editor: Shazib Pervaiz
Cancers 2021, 13(14), 3602;
Received: 29 May 2021 / Revised: 4 July 2021 / Accepted: 14 July 2021 / Published: 18 July 2021
Lineage plasticity is the ability of cells to transform from one cell type to another and is an important part for tissue repair and for maintenance of homeostasis. Unfortunately, the very same processes can be corrupted in cancer when the molecular checkpoints controlling the process are compromised; as a result of which treatment resistance and disease recurrence can emerge. It can be triggered by treatment received and has been seen across solid and liquid tumors. This review discusses the factors that control different manifestations of lineage plasticity in various cancer types and more importantly, discusses ideas to potentially revert this phenomenon.
Lineage plasticity, the switching of cells from one lineage to another, has been recognized as a cardinal property essential for embryonic development, tissue repair and homeostasis. However, such a highly regulated process goes awry when cancer cells exploit this inherent ability to their advantage, resulting in tumorigenesis, relapse, metastasis and therapy resistance. In this review, we summarize our current understanding on the role of lineage plasticity in tumor progression and therapeutic resistance in multiple cancers. Lineage plasticity can be triggered by treatment itself and is reported across various solid as well as liquid tumors. Here, we focus on the importance of lineage switching in tumor progression and therapeutic resistance of solid tumors such as the prostate, lung, hepatocellular and colorectal carcinoma and the myeloid and lymphoid lineage switch observed in leukemias. Besides this, we also discuss the role of epithelial-mesenchymal transition (EMT) in facilitating the lineage switch in biphasic cancers such as aggressive carcinosarcomas. We also discuss the mechanisms involved, current therapeutic approaches and challenges that lie ahead in taming the scourge of lineage plasticity in cancer. View Full-Text
Keywords: lineage plasticity; tumor progression; metastasis; therapy resistance; epithelial-mesenchymal plasticity lineage plasticity; tumor progression; metastasis; therapy resistance; epithelial-mesenchymal plasticity
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MDPI and ACS Style

Thankamony, A.P.; Subbalakshmi, A.R.; Jolly, M.K.; Nair, R. Lineage Plasticity in Cancer: The Tale of a Skin-Walker. Cancers 2021, 13, 3602.

AMA Style

Thankamony AP, Subbalakshmi AR, Jolly MK, Nair R. Lineage Plasticity in Cancer: The Tale of a Skin-Walker. Cancers. 2021; 13(14):3602.

Chicago/Turabian Style

Thankamony, Archana P., Ayalur Raghu Subbalakshmi, Mohit Kumar Jolly, and Radhika Nair. 2021. "Lineage Plasticity in Cancer: The Tale of a Skin-Walker" Cancers 13, no. 14: 3602.

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