CXCL2 promoted lymphatic metastasis in endometrial cancer by regulating STMN1 related ferroptosis

Abstract

Abstract CAFs infiltration increased and ferroptosis decreased in metastatic tissues and lymph nodes compared with non-metastatic endometrial cancer tissues and negative lymph nodes. The ferroptosis-related gene STMN1 was identified by bioinformatics analysis and was closely related to CAFs infiltration. Three STMN1 knockdown endometrial cancer cell lines were constructed to verify the attenuated malignant phenotype and increased ferroptosis. Supernatants of CAFs derived from non-metastatic tissues and metastatic lymphoid tissues were collected for cytokine chip detection. CXCL2 was identified to be closely related to the ferroptosis process of endometrial cancer. Detection of CXCL2 levels in clinical samples showed that CXCL2 levels were increased in tissues, serum and lymphoid tissues of patients with metastatic endometrial cancer. CXCL2 can partially rescue cancer cells from ferroptosis caused by STMN1 knockdown, restore the malignant phenotype, and enhance the tube formation ability of HLEC cells. In vivo experiments showed that CXCL2 promoted cancer cell tumorigenesis and metastasis, while knockdown of STMN1 attenuated this property. In summary, we demonstrated that CXCL2 secreted by CAFs from metastatic tissues regulated STMN1 to inhibit ferroptosis in cancer cells and promote tube formation in HLEC cells. These two synergetic effects promote lymphatic metastasis in endometrial cancer.