Chen Hongjie, Haddadi Nahal, Zhu Xiaofeng, Hatoum Diana, Chen Size, Nassif Najah T, Lin Yiguang, McGowan Eileen M
Department of Traditional Chinese Medicine, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
School of Life Sciences, University of Technology Sydney, Broadway, NSW, Australia.
J Oncol. 2022 Dec 7;2022:2250407. doi: 10.1155/2022/2250407. eCollection 2022.
Overexpression of sphingosine kinase 1 (SphK1) is casually associated with many types of cancer, and inhibitors of SphK1 sensitize tumors to chemotherapy. SphK1 is expressed as two major isoforms, SphK1a and SphK1b. To date, no information has been reported on the SphK1 isoform expression profile and its clinical relevance.
The objective is to examine the expression profile of the SphK1a and SPhK1b isoforms in human cancer and noncancer tissues and cell lines and explore their clinical relevance.
We used PCR to qualitatively examine the expression profile of these two isoforms in breast, liver, and prostate cancer tissues plus paired adjacent tissues and in 11 cancer and normal cell lines (breast, cervical, bone, prostate, colon, brain, mesothelioma tumor and benign, and human kidney cells).
We found that SphK1a was ubiquitously expressed in all cancer cells and tissues tested; in contrast, SphK1b was only expressed in selective cell types in breast, prostate, and lung cancer.
Our data suggest that SphK1a is important for generic SphK1/S1P functions, and SphK1b mediates specialized and/or unique pathways in a specific type of tissue and could be a biomarker for cancer. This discovery is important for future SphK1-related cancer research and may have clinical implications in drug development associated with SphK1-directed cancer treatment.
鞘氨醇激酶1（SphK1）的过表达与多种癌症偶然相关，且SphK1抑制剂可使肿瘤对化疗敏感。SphK1以两种主要亚型SphK1a和SphK1b的形式表达。迄今为止，尚未有关于SphK1亚型表达谱及其临床相关性的报道。
研究SphK1a和SphK1b亚型在人类癌症组织、非癌组织及细胞系中的表达谱，并探讨其临床相关性。
我们采用聚合酶链反应（PCR）定性检测这两种亚型在乳腺癌、肝癌和前列腺癌组织及其配对的相邻组织，以及11种癌症和正常细胞系（乳腺癌、宫颈癌、骨癌、前列腺癌、结肠癌、脑癌、间皮瘤肿瘤及良性肿瘤细胞系和人肾细胞）中的表达谱。
我们发现SphK1a在所有检测的癌细胞和组织中均普遍表达；相比之下，SphK1b仅在乳腺癌、前列腺癌和肺癌的特定细胞类型中表达。
我们的数据表明，SphK1a对SphK1/鞘氨醇-1-磷酸（S1P）的一般功能很重要，而SphK1b在特定类型的组织中介导特殊和/或独特的信号通路，可能是一种癌症生物标志物。这一发现对未来与SphK1相关的癌症研究具有重要意义，可能对与SphK1导向的癌症治疗相关的药物开发具有临床意义。
