Acquisition of Anoikis Resistance Up-regulates Caveolin-1 Expression in Human Non-small Cell Lung Cancer Cells

Background: Anoikis is a key inhibitory step in the process of cancer cell metastasis. Knowledge regarding the adaptive response resulting in resistance to anoikis may benefit the development of new therapies. Materials and Methods: Anoikis-resistant cells were generated from anoikis-sensitive lung carcinoma cells and the underlying mechanism for this process was investigated. Results: Culturing H460 cells under suspended conditions caused spontaneous generation of anoikis-resistant H_AR1 and H_AR2 cells. We found that anoikis resistance in these cells caused caveolin-1 (CAV1) up-regulation. Using short hairpin RNA (shRNA), we confirmed that depletion of CAV1 rendered anoikis-resistant H_AR2 cells sensitive to anoikis. Furthermore, this study revealed that the acquisition of anoikis resistance induced CAV1 up-regulation through induction of CAV1 mRNA transcription. Conclusion: Our findings show CAV1 to be a key player in anoikis resistance and provide a novel mechanism regarding cancer cell adaptation, resulting in acquisition of anoikis resistance in lung cancer cells.