J Korean Med Sci.  2024 May;39(19):e156. 10.3346/jkms.2024.39.e156.

Anchorage Dependence and Cancer Metastasis

• Lee DK
• Oh J
• Park HW
• Gee HY

• KMID: 2555912
• DOI: http://doi.org/10.3346/jkms.2024.39.e156

Abstract

The process of cancer metastasis is dependent on the cancer cells’ capacity to detach from the primary tumor, endure in a suspended state, and establish colonies in other locations. Anchorage dependence, which refers to the cells’ reliance on attachment to the extracellular matrix (ECM), is a critical determinant of cellular shape, dynamics, behavior, and, ultimately, cell fate in nonmalignant and cancer cells. Anchorage-independent growth is a characteristic feature of cells resistant to anoikis, a programmed cell death process triggered by detachment from the ECM. This ability to grow and survive without attachment to a substrate is a crucial stage in the progression of metastasis. The recently discovered phenomenon named “adherent-to-suspension transition (AST)” alters the requirement for anchoring and enhances survival in a suspended state. AST is controlled by four transcription factors (IKAROS family zinc finger 1, nuclear factor erythroid 2, BTG anti-proliferation factor 2, and interferon regulatory factor 8) and can detach cells without undergoing the typical epithelialmesenchymal transition. Notably, AST factors are highly expressed in circulating tumor cells compared to their attached counterparts, indicating their crucial role in the spread of cancer. Crucially, the suppression of AST substantially reduces metastasis while sparing primary tumors. These findings open up possibilities for developing targeted therapies that inhibit metastasis and emphasize the importance of AST, leading to a fundamental change in our comprehension of how cancer spreads.

Keyword

Metastatic Cascade; Anchorage Independence; Circulating Tumor Cell; Adherent-to-Suspension Transition

Figure

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  Fig. 1 Schematic representation of anchorage-dependent growth and anchorage-independent growth. The intercellular bridge protein depicted in the diagram is a generalized intercellular component of junctional complexes. In this context, normal cells that detach from the extracellular matrix undergo anoikis. However, malignant cells are capable of evading anoikis, enabling them to circulate as tumor cells in the blood stream (CTCs).CTC = circulating tumor cell.

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  Fig. 2 Schematic representation of AST in the metastatic cascade. Ectopic expression of the four factors IKZF1, NFE2, BTG2 and IRF8 induce anchorage-independent growth by suppressing the YAP/TEAD pathway and inducing expression of hemoglobin genes. The induction of AST leads to metastatic dissemination of circulating tumor cells.AST = adhesion-to-suspension transition, IKZF1 = IKAROS family zinc finger 1, NFE2 = nuclear factor erythroid 2, BTG2 = BTG anti-proliferation factor 2, IRF8 = interferon regulatory factor 8.

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