Anoikis is a form of cell death regulated by integrin-dependent ECM signaling, playing a crucial role in cell fate and physiological processes. It is defined as an intrinsic apoptosis triggered by loss of ECM attachment, and is involved in embryonic development, tissue repair, inflammatory responses, cardiovascular diseases, and tumor metastasis. Anoikis is also critical in stem cell research, influencing in vitro cell culture models, stem cell therapy, and engineering applications. The molecular mechanisms of anoikis involve integrins, which transmit ECM signals to the cell, and are regulated by various signaling pathways, including the intrinsic and extrinsic apoptosis pathways. Anoikis resistance is essential for tumor metastasis and is influenced by factors such as ECM alterations, cell adhesion, and integrin signaling. In therapeutic interventions, anoikis regulation offers potential strategies for drug therapy and cell-based therapy, targeting pathways such as NF-κB, PI3K/Akt, STAT3, and others. Integrin-based therapies are also being explored, with several drugs targeting specific integrin dimers in clinical trials. Anoikis is a key factor in disease progression, drug resistance, and stem cell survival, and its regulation through molecular and ECM signaling provides new strategies for therapeutic interventions. Understanding the mechanisms of anoikis is essential for developing effective treatments for various diseases, including cancer and other pathological conditions.Anoikis is a form of cell death regulated by integrin-dependent ECM signaling, playing a crucial role in cell fate and physiological processes. It is defined as an intrinsic apoptosis triggered by loss of ECM attachment, and is involved in embryonic development, tissue repair, inflammatory responses, cardiovascular diseases, and tumor metastasis. Anoikis is also critical in stem cell research, influencing in vitro cell culture models, stem cell therapy, and engineering applications. The molecular mechanisms of anoikis involve integrins, which transmit ECM signals to the cell, and are regulated by various signaling pathways, including the intrinsic and extrinsic apoptosis pathways. Anoikis resistance is essential for tumor metastasis and is influenced by factors such as ECM alterations, cell adhesion, and integrin signaling. In therapeutic interventions, anoikis regulation offers potential strategies for drug therapy and cell-based therapy, targeting pathways such as NF-κB, PI3K/Akt, STAT3, and others. Integrin-based therapies are also being explored, with several drugs targeting specific integrin dimers in clinical trials. Anoikis is a key factor in disease progression, drug resistance, and stem cell survival, and its regulation through molecular and ECM signaling provides new strategies for therapeutic interventions. Understanding the mechanisms of anoikis is essential for developing effective treatments for various diseases, including cancer and other pathological conditions.