Department of Radiotherapy and Oncology, The Affiliated Hospital of Jiangnan University, Wuxi 214062, China.
Jiangnan University, Wuxi 214062, China.
Int J Biochem Cell Biol. 2024 Jan;166:106506. doi: 10.1016/j.biocel.2023.106506. Epub 2023 Dec 13.
Pyrroline-5-carboxylate reductase 2 (PYCR2) expression is aberrantly upregulated in colon cancer. However, the functions and underlying mechanisms of PYCR2 in breast cancer remain elusive. The primary objective of the present study was to elucidate the function of PYCR2 in breast cancer and investigate whether PYCR2 may be transcriptionally regulated by c-Myc to activate the AKT signaling pathway.
Immunohistochemical analysis was performed to examine the expression of PYCR2 in breast cancer and adjacent non-cancerous tissues. Western blot and RT-qPCR were utilized to detect PYCR2 expression in breast cancer cells. Cellular functionalities were evaluated through Transwell assays in vitro and lung metastasis formation assays in vivo. Moreover, the impact of PYCR2 on the activation of AKT signaling was determined through western blot and immunohistochemistry analysis. The transcriptional regulation of PYCR2 expression by c-Myc was evaluated via both western blot analysis and luciferase gene reporter assay.
PYCR2 overexpression was noted in breast cancer. Silencing PYCR2 expression attenuated the invasive and metastatic abilities of breast cancer cells. Furthermore, the activation of the AKT signaling pathway is indispensable for the promotion of invasion and metastasis mediated by PYCR2. Lastly, the binding of c-Myc to the promoter sequence of PYCR2 resulted in the upregulation of PYCR2 transcription.
Taken together, these results indicate that PYCR2 is transcriptionally regulated by c-Myc and promotes invasion and metastasis in breast cancer through the activation of the AKT pathway.
吡咯啉-5-羧酸还原酶 2（PYCR2）在结肠癌中表达异常上调。然而，PYCR2 在乳腺癌中的功能和潜在机制仍不清楚。本研究的主要目的是阐明 PYCR2 在乳腺癌中的功能，并研究 PYCR2 是否可能被 c-Myc 转录调控以激活 AKT 信号通路。
通过免疫组织化学分析检测 PYCR2 在乳腺癌和相邻非癌组织中的表达。Western blot 和 RT-qPCR 用于检测乳腺癌细胞中 PYCR2 的表达。通过体外 Transwell 测定和体内肺转移形成测定评估细胞功能。此外，通过 Western blot 和免疫组化分析确定 PYCR2 对 AKT 信号激活的影响。通过 Western blot 分析和荧光素酶基因报告测定评估 c-Myc 对 PYCR2 表达的转录调控。
PYCR2 在乳腺癌中过表达。沉默 PYCR2 表达可减弱乳腺癌细胞的侵袭和转移能力。此外，AKT 信号通路的激活对于 PYCR2 介导的侵袭和转移的促进是必不可少的。最后，c-Myc 与 PYCR2 启动子序列的结合导致 PYCR2 转录的上调。
综上所述，这些结果表明，PYCR2 受 c-Myc 转录调控，并通过激活 AKT 通路促进乳腺癌的侵袭和转移。
