Department of Medical Oncology, Dr BRA IRCH, AIIMS, New Delhi, 110029, India.
Department of Pathology, AIIMS, New Delhi, 110029, India.
Exp Cell Res. 2020 Nov 1;396(1):112282. doi: 10.1016/j.yexcr.2020.112282. Epub 2020 Sep 11.
In the present study, we have explored the prognostic value of the Phosphofructokinase Platelet-type (PFKP) expression and its therapeutic relevance in metastatic breast cancer. PFKP immunohistochemistry was performed on Invasive ductal carcinomas (IDCs; n = 87) of breast, and its association with clinicopathological parameters were evaluated. Using online meta-analysis tools, PFKP's prognostic value was investigated in overall breast cancer as well as in triple negative subtype (TNBCs). For in vitro analysis, MDA-MB-231 cells model was used in order to elucidate mechanisms behind PFKP regulated glycolysis and its impact on cancer cell physiology. Therapeutic relevance of PFKP was further evaluated using PFKP siRNA and Quercetin. PFKP protein expression was found to be positively associated with nodal invasion (p = 0.009), receptor (ER & PR) negative status (p = 0.005 & p = 0.028) and reduced overall survival in breast cancer patients (p = 0.014). In MDA-MB-231 cells, quercetin treatment impaired PFKP-LDHA signaling axis thereby inhibiting aerobic glycolysis mediated increased migration of cancer cells. Our present study demonstrates that elevated PFKP levels are associated with basal cells/TNBC subtypes and might serve as prognostic indicator for TNBC patients. Ability of quercetin to inhibit aerobic glycolysis, cell migration and clonogenic potential of malignant breast cancer cells advocates possibility of quercetin in aggressive breast cancer treatment.
在本研究中，我们探讨了磷酸果糖激酶血小板型（PFKP）表达的预后价值及其在转移性乳腺癌中的治疗相关性。对 87 例乳腺浸润性导管癌（IDC）进行了 PFKP 免疫组织化学染色，并评估了其与临床病理参数的相关性。使用在线荟萃分析工具，研究了 PFKP 在总体乳腺癌以及三阴性乳腺癌（TNBC）中的预后价值。为了阐明 PFKP 调节糖酵解的机制及其对癌细胞生理的影响，我们在 MDA-MB-231 细胞模型中进行了体外分析。进一步使用 PFKP siRNA 和槲皮素评估了 PFKP 的治疗相关性。研究发现，PFKP 蛋白表达与淋巴结侵犯（p=0.009）、受体（ER 和 PR）阴性状态（p=0.005 和 p=0.028）呈正相关，并与乳腺癌患者的总生存时间缩短相关（p=0.014）。在 MDA-MB-231 细胞中，槲皮素治疗可损害 PFKP-LDHA 信号轴，从而抑制有氧糖酵解介导的癌细胞迁移增加。本研究表明，PFKP 水平升高与基底细胞/TNBC 亚型相关，可能作为 TNBC 患者的预后指标。槲皮素抑制有氧糖酵解、细胞迁移和恶性乳腺癌细胞的克隆形成能力，提示槲皮素在侵袭性乳腺癌治疗中的可能性。
