Copper-cysteamine nanoparticle-mediated microwave dynamic therapy promotes colorectal cancer metastasis by inhibiting promoting ferroptosis via downregulating PTK2B

Abstract

Cancer metastasis stands as the primary cause of cancer-related deaths. Recent studies highlight the role of ferroptosis in inhibiting cancer metastasis. In our prior research, we discovered that Cu-Cy-mediated Microwave Dynamic Therapy (MWDT) triggered ferroptosis in colorectal cancer (CRC) cells, leading to reduced cell proliferation. However, the impact of MWDT on tumor metastasis remains unclear, as does the mechanism behind induced iron death. This study aimed to elucidate the effects of MWDT on CRC cell metastasis and uncover the underlying mechanisms. Our findings reveal that MWDT effectively suppresses CRC cell metastasis and significantly decreases PTK2B expression. Functional analyses demonstrate that altering PTK2B expression levels can modulate CRC cell proliferation, migration, and invasion. Further investigations unveil PTK2B's regulation of GPX4 and ACSL4 expression, which in turn influences LPO and MDA levels. Targeted overexpression of PTK2B attenuates MWDT's pro-ferroptosis effect and partially reverses its inhibitory effects on tumor cell metastasis and proliferation. Collectively, these results suggest that MWDT inhibits CRC progression and metastasis through PTK2B-mediated ferroptosis, presenting a novel therapeutic approach for metastatic cancer.