Pancreatic cancer remains a significant health burden associated with limited patient survival and poses a major therapeutic challenge. Among cancer cells, Cancer stem cells (CSCs) are instrumental in inducing chemoresistance and metastasis in pancreatic cancer. CD133 has been identified as a CSC surface marker in several malignancies including pancreatic cancer. However, the functional role of CD133 in CSCs still not clear. The present study investigates the role of caveolar lipid raft integrity in functional properties of CD133+ CSCs. Current study showed first time that CD133 localizes to caveolar lipid rafts in pancreatic cancer cells, and associates with Caveolin1 (Cav-1) and cholesterol to form an integral signaling complex which drives the downstream processes of chemoresistance and metastasis. Further analysis showed that the integrity of the lipid-raft is crucial for maintenance of the functional properties of pancreatic CSCs, and its disruption leads to increased chemo-sensitivity to chemotherapeutic compound paclitaxel both in vitro as well as in vivo. Additionally, disruption of lipid raft results in decreased invasiveness and metastatic ability of the cells by deregulation of FAK signaling. The study also reveals that pancreatic cancer cells that lack the CSC population marker, CD133, did not respond to lipid raft disruption. Our results indicated that targeting the lipid-raft integrity in pancreatic cancer can specifically eradicate the CD133+ CSCs in pancreatic tumors, leading to a better prognosis for the disease.
Citation Format: Vineet K. Gupta, Nikita S. Sharma, Kousik Kesh, Patrcia Dauer, Alice Nomura, Bhuwan Giri, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee. Lipid raft integrity is essential for metastasis and chemoresistance properties of CD133+ cancer stem cells in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3551.