Targeting cancer cell adhesion molecule, CD146, with low-dose gold nanorods and mild hyperthermia disrupts actin cytoskeleton and cancer cell migration

Author: Jinyuan Liu, Department of Nanoscience and Nanoengineering

Mentor: Dr. Congzhou Wang, Department of Nanoscience and Nanoengineering

CD146, a cancer cell adhesion molecule, is over-expressed on the surfaces of metastatic melanoma, breast, ovarian and prostate cancer cells, and its over-expression is directly associated with the enhanced migration of these cancer cells and poor patient prognosis. In this work, we demonstrate that targeting CD146 with low-dose gold nanorods combined with mild hypothermia can completely stop the migration of two model metastatic cancer cells including a melanoma (SKMEL-2) and a breast cancer cell line (MDA-MB-231). Two nanoscale imaging tools, atomic force microscopy and direct stochastic optical reconstruction microscopy, reveal that the disruption of the actin cytoskeleton and the altered cell morphology correspond to the loss of cell migration. Further mechanistic analysis indicates that CD146 targeted gold nanorods and mild hyperthermia disrupt the actin cytoskeleton by a synergistic mechanism including depleting membrane CD146 and interfering ezrin-radixin-moesin phosphorylation, thus releasing the actin cytoskeleton from the cell membrane and compromising the force transduction through the actin cytoskeleton to the membrane CD146. As a result, we believe targeting CD146 with low-dose gold nanorods and mild hyperthermia could be a versatile, effective, and safe approach for stopping cancer metastasis. More broadly, the concept of targeting cancer cell surface markers that are directly linked to the actin cytoskeleton, represents a new way to alter the biophysical properties of the cancer cells and their associated metastatic ability, and could be appliable to other cancers.