Anoikis-Associated Lung Cancer Metastasis: Mechanisms and Therapies

SIMPLE SUMMARY: Anoikis is a programmed cell death process resulting from the loss of interaction between cells and the extracellular matrix. Therefore, it is necessary to overcome anoikis when tumor cells acquire metastatic potential. In lung cancer, the composition of the extracellular matrix, cell adhesion-related membrane proteins, cytoskeletal regulators, and epithelial–mesenchymal transition are involved in the process of anoikis, and the initiation of apoptosis signals is a critical step in anoikis. Inversely, activation of growth signals counteracts anoikis. This review summarizes the regulators of lung cancer-related anoikis and explores potential drug applications targeting anoikis. ABSTRACT: Tumor metastasis occurs in lung cancer, resulting in tumor progression and therapy failure. Anoikis is a mechanism of apoptosis that combats tumor metastasis; it inhibits the escape of tumor cells from the native extracellular matrix to other organs. Deciphering the regulators and mechanisms of anoikis in cancer metastasis is urgently needed to treat lung cancer. Several natural and synthetic products exhibit the pro-anoikis potential in lung cancer cells and in vivo models. These products include artonin E, imperatorin, oroxylin A, lupalbigenin, sulforaphane, renieramycin M, avicequinone B, and carbenoxolone. This review summarizes the current understanding of the molecular mechanisms of anoikis regulation and relevant regulators involved in lung cancer metastasis and discusses the therapeutic potential of targeting anoikis in the treatment of lung cancer metastasis.