SPAG5 upregulation predicts poor prognosis in cervical cancer patients and alters sensitivity to taxol treatment via the mTOR signaling pathway

Abstract

Previously, we found that sperm-associated antigen 5 (SPAG5) was upregulated in pelvic lymph node metastasis–positive cervical cancer. The aim of this study is to examine the role of SPAG5 in the proliferation and tumorigenicity of cervical cancer and its clinical significance in tumor progression. In our study, SPAG5 expression in cervical cancer patients was detected using quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry; cervical cancer cell function with downregulated SPAG5 in vitro was explored using tetrazolium assay, flow cytometry, and colony formation and Transwell assays. SPAG5 was upregulated in tumor tissue compared with paired adjacent noncancerous tissues; SPAG5 upregulation in tumor tissues indicated poor disease-free survival, which was also an independent prognostic indicator for cervical cancer patients. In vitro study demonstrated that SPAG5 downregulation inhibited cell proliferation and growth significantly by G2/M arrest and induction of apoptosis, and hindered cell migration and invasion. Under SPAG5 downregulation, the sensitivity of cervical cancer cells differed according to taxol dose, which correlated with mammalian target of rapamycin (mTOR) signaling pathway activity. In general, SPAG5 upregulation relates to poor prognosis in cervical cancer patients, and SPAG5 is a regulator of mTOR activity during taxol treatment in cervical cancer.

High expression of SPAG5 sustains the malignant growth and invasion of breast cancer cells through the activation of Wnt/β‐catenin signalling

“…Illumina whole‐genome gene expression microarrays show that SPAG5 expression is highly up‐regulated in non‐small‐cell lung cancer tissues . High levels of SPAG5 in cervical cancer patients predict poor disease‐free survival . In prostate cancer, SPAG5 expression is gradually increased in prostate cancer progression and the high expression of SPAG5 is correlated with clinical stage, Gleason score, lymph node metastasis, and biochemical recurrence .…”

“…Notably, recent studies have reported an important role of SPAG5 in cancers. High expression of SPAG5 is frequently detected in cancer tissues and is correlated with tumour progression and poor prognosis . SPAG5 is involved in regulating the proliferation, apoptosis, migration and invasion of tumour cells .…”

SPAG5 as a prognostic biomarker and chemotherapy sensitivity predictor in breast cancer: a retrospective, integrated genomic, transcriptomic, and protein analysis

“…Given that drugs such as the anthracyclines and taxane, which interfere with the normal progression of mitosis, belong to the most successful chemotherapeutic compounds that are currently used for anticancer treatment, SPAG5 could be a molecular target on which the development of "next generation anti-mitotic drugs" could be based. Recent studies in cervical cancer 34,35 reported SPAG5 to be up-regulated, and demonstrated that the downregulation of SPAG5 inhibited cell proliferation/growth, increased apoptosis and hindered cell migration and invasion. 35 Furthermore, it is possible that "anti-SPAG5…”

“…Recent studies in cervical cancer 34,35 reported SPAG5 to be up-regulated, and demonstrated that the downregulation of SPAG5 inhibited cell proliferation/growth, increased apoptosis and hindered cell migration and invasion. 35 Furthermore, it is possible that "anti-SPAG5…”

“…35 Furthermore, it is possible that "anti-SPAG5 agents" could sensitize resistant BC cells to current treatment regimens.…”