Department of Pharmaceutical Engineering, Catholic University of Daegu, Gyungsan, 38430, South Korea.
Department of Biomedical Science, Catholic University of Daegu, Gyungsan, 38430, South Korea.
Biochem Biophys Res Commun. 2021 Jun 18;558:22-28. doi: 10.1016/j.bbrc.2021.04.054. Epub 2021 Apr 22.
Autocrine motility factor (AMF) stimulates the motility of cancer cells via an autocrine route and has been implicated in tumor progression and metastasis. Overexpression of AMF is correlated with the aggressive nature of breast cancer and is negatively associated with clinical outcomes. In contrast, AMF also has the ability to suppress cancer cells. In this study, AMFs from different cancer cells were demonstrated to have suppressive activity against MCF-7 and MDA-MB-231 breast cancer cells. In a growth and colony formation assay, AMF from AsPC-1 pancreatic cancer cells (ASPC-1:AMF) was determined to be more suppressive compared to other AMFs. It was also demonstrated that AsPC-1:AMF could arrest breast cancer cells at the G0/G1 cell cycle phase. Quantified by Western blot analysis, AsPC-1:AMF lowered levels of the AMF receptor (AMFR) and G-protein-coupled estrogen receptor (GPER), concomitantly regulating the activation of the AKT and ERK signaling pathways. JAK/STAT activation was also decreased. These results were found in estrogen receptor (ER)-positive MCF-7 cells but not in triple-negative MDA-MB-231 cells, suggesting that AsPC-1:AMF could work through multiple pathways led to apoptosis. More importantly, AsPC-1:AMF and methyl jasmonate (MJ) cooperatively and synergistically acted against breast cancer cells. Thus, AMF alone or along with MJ may be a promising breast cancer treatment option.
自分泌运动因子（AMF）通过自分泌途径刺激癌细胞的运动，并与肿瘤的进展和转移有关。AMF 的过表达与乳腺癌的侵袭性有关，并与临床结果呈负相关。相反，AMF 也具有抑制癌细胞的能力。在这项研究中，来自不同癌细胞的 AMFs 被证明对 MCF-7 和 MDA-MB-231 乳腺癌细胞具有抑制活性。在生长和集落形成测定中，与其他 AMFs 相比，来自胰腺癌细胞（AsPC-1:AMF）的 AMF 被确定具有更强的抑制作用。还表明，AsPC-1:AMF 可以使乳腺癌细胞停滞在 G0/G1 细胞周期阶段。通过 Western blot 分析定量，AsPC-1:AMF 降低了 AMF 受体（AMFR）和 G 蛋白偶联雌激素受体（GPER）的水平，同时调节 AKT 和 ERK 信号通路的激活。JAK/STAT 激活也减少了。这些结果在雌激素受体（ER）阳性的 MCF-7 细胞中发现，但在三阴性 MDA-MB-231 细胞中未发现，表明 AsPC-1:AMF 可能通过多种途径导致细胞凋亡。更重要的是，AsPC-1:AMF 和茉莉酸甲酯（MJ）协同作用，协同作用于乳腺癌细胞。因此，AMF 单独或与 MJ 联合使用可能是一种有前途的乳腺癌治疗选择。
