Mechanistic insights into mesenchymal-amoeboid transition as an intelligent cellular adaptation in cancer metastasis and resistance.

Malignant cell plasticity is an important hallmark of tumor biology and crucial for metastasis and resistance. Cell plasticity lets cancer cells adapt to and escape the therapeutic strategies, which is the leading cause of cancer patient mortality. Epithelial cells acquire mobility via epithelial-mesenchymal transition (EMT), whereas mesenchymal cells enhance their migratory ability and clonogenic potential by acquiring amoeboid characteristics through mesenchymal-amoeboid transition (MAT). Tumor formation, progression, and metastasis depend on the tumor microenvironment (TME), a complex ecosystem within and around a tumor. Through increased migration and metastasis of cancer cells, the TME also contributes to malignancy. This review underscores the distinction between invasion pattern morphological manifestations and the diverse structures found within the TME. Furthermore, the mechanisms by which amoeboid-associated characteristics promote resistance and metastasis and how these mechanisms may represent therapeutic opportunities are discussed. In metastasis and resistance, cancer cells use the mesenchymal-amoeboid transition (MAT) to adapt. During this process, cancer cells switch from mesenchymal (elongated, matrix-degrading) to amoeboid (blebbed, rounded, contractility-driven, fast-moving) migration phenotypes. Cancer cells benefit from this adaptability by overcoming various microenvironmental challenges and facilitating invasion, dissemination, and survival (Created with BioRender.com). [Display omitted] • MAT, mesenchymal-amoeboid transition, enhances cancer metastasis and resistance. • Amoeboid phenotype: rounded shape, blebs, heightened actomyosin contractility, reduced adhesions. • Amoeboid cancer cells migrate faster than mesenchymal counterparts. • Amoeboid cancer cells exhibit stem-like properties and heightened treatment resistance. • Tumor microenvironment influences MAT, with decreased adhesion sites and increased confinement driving the transition. [ABSTRACT FROM AUTHOR]