关键词: 乳腺癌, 线粒体, 肉碱棕榈酰转移酶1A, 细胞外信号调节激酶, 恶性行为

Abstract:

Background and purpose: The overexpression of carnitine palmitoyl transferase 1A (CPT1A) is related to the poor prognosis of breast cancer, and it can promote the utilization of fatty acids by mitochondria and maximize triphosphate (ATP) production. However, the role of CPT1A in breast cancer metastasis is still unclear. This study aimed to explore the mechanism that mitochondrial dysfunction and CPT1A/extracellular signal-regulated kinase (ERK) signaling pathway in breast cancer jointly regulate the malignant behavior of breast cancer. Methods: The lentivirus system and shRNA tools were used to overexpress or knock down CPT1A in human breast cancer cell lines MDA-MB-231 and MCF7, and the cells were divided into NC group, CPT1A group and shCPT1A group. The invasion ability of cells was detected by transwell assay, and the protein expressions of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), ERK1/2 and CPT1A were analyzed by Western blot. The mitochondrial morphology of MDA-MB-231 and MCF7 cell lines was analyzed using mitochondrial red staining, and mitochondrial respiratory capacity was analyzed by oxygen consumption rate. Results: Compared with cells expressing control vector, overexpression of CPT1A resulted in enhanced invasion abilities of MCF7 cells and MDA-MB-231 cells (P<0.05), while knockdown of shCPT1A resulted in decreased invasion abilities of cells (P<0.05). Compared with NC group, the length of mitochondrial branches in MDA-MB-231 and MCF7 cells in CPT1A group was significantly shorter (P<0.05), and the expressions of ERK1/2 and PGC-1α increased significantly (P <0.05). In shCPT1A group, the length of mitochondrial branches in MDA-MB-231 and MCF7 cells increased significantly (P <0.05), and the expressions of ERK1/2 and PGC-1α decreased significantly (P<0.05). In addition, compared with NC group, the cellular basis, maximum respiratory capacity and ATP production of MDA-MB-231 in CPT1A group increased significantly (P <0.05), while the cellular basis, maximum respiratory capacity and ATP production of MDA-MB-231 in shCPT1A group decreased significantly (P<0.05). Conclusion: ERK1/2-PGC-1α activated by CPT1A Signaling pathway plays a key role in mitochondrial division mediated breast cancer cell metastasis.

Key words: Breast cancer, Mitochondria, Carnitine palmitoyl transferase 1A, Extracellular signal-regulated kinase, Malignant behavior