Comprehensive understanding of anchorage-independent survival and its implication in cancer metastasis

Abstract

Detachment is the initial and critical step for cancer metastasis. Only the cells that survive from detachment can develop metastases. Following the disruption of cell–extracellular matrix (ECM) interactions, cells are exposed to a totally different chemical and mechanical environment. During which, cells inevitably suffer from multiple stresses, including loss of growth stimuli from ECM, altered mechanical force, cytoskeletal reorganization, reduced nutrient uptake, and increased reactive oxygen species generation. Here we review the impact of these stresses on the anchorage-independent survival and the underlying molecular signaling pathways. Furthermore, its implications in cancer metastasis and treatment are also discussed.

Cycloartocarpin Inhibits Migration through the Suppression of Epithelial-to-Mesenchymal Transition and FAK/AKT Signaling in Non-Small-Cell Lung Cancer Cells

“…The anchorage-independent growth of cancer cells represents both the ability of malignant tumor cells to spread and the resistance to anoikis [ 20 , 21 ]. Thus, we examined how cycloartocarpin affected cell growth and survival in detachment circumstances.…”

“…EMT is a biological mechanism that has been closely linked to cancer progression and metastasis. It is also known to promote cancer cell motility, invasion, anoikis resistance, and cancer stem cells in lung cancer [ 6 , 20 , 21 ]. As a result, we first looked into the EMT makers in cells treated with cycloartocarpin to assess the underlying mechanism.…”

Human epidermal growth factor receptor 3 serves as a novel therapeutic target for acral melanoma

“…We also analyzed other signaling molecules that are reported to regulate anchorage-independent growth of various tumor cells [41]: Akt (downstream of PI3K), proto-oncogene tyrosine-protein kinase Src (Src), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK). No signi cant changes were observed in the phosphorylation status of these signaling molecules in AM cells (Supplementary Figs.…”

Contribution of integrin adhesion to cytokinetic abscission and genomic integrity

“…A characteristic feature of cancer cells is their ability to complete cytokinesis without integrin adhesion, which may facilitate colony formation at foreign locations during metastatic spreading ( Thullberg M et al, 2007 ; Pellinen T et al, 2008 ; Desgrosellier and Cheresh, 2010 ; Deng Z et al, 2021 ). Identification of the adhesion-independent cytokinesis mechanism(s) used by cancer cells is of interest, particularly since it may potentially lead to the identification of tumor-specific treatment targets.…”

“…The integrin adhesion-dependent FAK-Src activation is a long-known requirement for sustained induction of the PI3K-Akt and the Ras-ERK pathways needed to avoid apoptosis and to pass the G1-S checkpoint of the cell cycle ( Schwartz and Assoian, 2001 ; Reddig and Juliano, 2005 ). The absence of the adhesion will efficiently stop proliferation unless the checkpoint is suppressed by viruses or mutations ( Thullberg and Stromblad, 2008 ; Deng Z et al, 2021 ; Engeland K, 2022 ). More recently, integrin signals via FAK have been found to contribute to cytokinetic abscission ( Reverte C G et al, 2006 ; Thullberg M et al, 2007 ; Pellinen T et al, 2008 ; Kamranvar S A et al, 2016 ), as well as to the arrangement of centrosomes into a bipolar mitotic spindle which is also essential for successful cytokinesis ( Park A Y et al, 2009 ; Kamranvar S A et al, 2022b ).…”