SPAG5 upregulation predicts poor prognosis in cervical cancer patients and alters sensitivity to taxol treatment via the mTOR signaling pathway.
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.
1] State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China [2] Department of Gynecology, Sun Yat-sen University Cancer Center; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
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LJ
Yuan
1] State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China [2] Department of Gynecology, Sun Yat-sen University Cancer Center; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
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JD
Li
1] State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China [2] Department of Gynecology, Sun Yat-sen University Cancer Center; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
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L
Zhang
Department of Chest, Second People's Hospital of Guangdong Province, Guangzhou 510317, China.
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JH
Wang
1] State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China [2] Department of Gynecology, Sun Yat-sen University Cancer Center; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
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T
Wan
1] State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China [2] Department of Gynecology, Sun Yat-sen University Cancer Center; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
Y
Y
Zhou
1] State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China [2] Department of Gynecology, Sun Yat-sen University Cancer Center; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
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H
Tu
Department of Pathology, Sun Yat-sen University Cancer Center; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
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JP
Yun
Department of Pathology, Sun Yat-sen University Cancer Center; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
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RZ
Luo
State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
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WH
Jia
1] State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China [2] Department of Gynecology, Sun Yat-sen University Cancer Center; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
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M
Zheng
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D009361:Neoplasm Invasiveness; D017239:Paclitaxel / Q000494:pharmacology*; D034622:RNA Interference; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; C486663:SPAG5 protein, human; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D017239:Paclitaxel