Department of Dermatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011 Shanghai, China.
State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 200032 Shanghai, China.
Discov Med. 2024 Aug;36(187):1692-1702. doi: 10.24976/Discov.Med.202436187.155.
Cutaneous squamous cell carcinoma (cSCC) is a fatal disease characterized by metabolic dysregulation. The role of ephrin type-B receptor 2 (ephrin-B2), a crucial molecule in cancer cell biology, in regulating glycolysis and cell proliferation of cSCC is not well understood. This study aimed to investigate the biological pathways by which ephrin-B2 impacts the glycolysis and cell proliferation of cSCC.
Ephrin-B2 expression levels in cSCC were determined using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting. expression in cSCC cells was manipulated using overexpression and knockdown approaches. A series of assays, such as cell counting kit-8 (CCK-8), Transwell assay, immunofluorescence assay, enzyme-linked immunosorbent assay (ELISA), qRT-PCR, and Western blotting, were employed to delineate the biological roles of ephrin-B2/pyruvate kinase muscle isoenzyme 2 (PKM2)/hypoxia-inducible factor 1 alpha (HIF-1α) in proliferation, migration, invasion, and glucose metabolism of cSCC.
This study highlights an upregulation of expression in cSCC. Knockdown of significantly suppressed the proliferation, migration, invasion, and glucose metabolism of cSCC cells. Moreover, expression was upregulated under hypoxic conditions. At the molecular level, knockdown resulted in the downregulation of and expression. Additionally, the overexpression of or successfully rescued the diminished proliferation, migration, invasion and glucose metabolism induced by knockdown in cSCC cells.
These findings suggest that ephrin-B2 suppression may hinder cSCC cell proliferation and glycolytic metabolism, potentially via the PKM2/HIF-1α axis modulation.
皮肤鳞状细胞癌（cSCC）是一种以代谢失调为特征的致命疾病。在癌症细胞生物学中，ephrin 型-B 受体 2（ephrin-B2）是一个关键分子，但其在调节 cSCC 的糖酵解和细胞增殖中的作用尚不清楚。本研究旨在探讨 ephrin-B2 影响 cSCC 糖酵解和细胞增殖的生物学途径。
采用定量逆转录聚合酶链反应（qRT-PCR）和 Western blot 检测 cSCC 中 ephrin-B2 的表达水平。采用过表达和敲低方法操纵 cSCC 细胞中的表达。通过一系列细胞计数试剂盒-8（CCK-8）、Transwell 测定、免疫荧光测定、酶联免疫吸附测定（ELISA）、qRT-PCR 和 Western blot 等实验，阐明 ephrin-B2/丙酮酸激酶肌肉同工酶 2（PKM2）/缺氧诱导因子 1 ɑ（HIF-1α）在 cSCC 增殖、迁移、侵袭和葡萄糖代谢中的生物学作用。
本研究强调了 cSCC 中表达上调。 敲低显著抑制了 cSCC 细胞的增殖、迁移、侵袭和葡萄糖代谢。此外，在缺氧条件下表达上调。在分子水平上， 敲低导致和表达下调。此外，过表达 或 成功挽救了 cSCC 细胞中 敲低导致的增殖、迁移、侵袭和葡萄糖代谢减少。
这些发现表明，ephrin-B2 抑制可能通过 PKM2/HIF-1α 轴的调节来阻碍 cSCC 细胞的增殖和糖酵解代谢。
