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The inhibition of HeLa cells proliferation through SPARCL1 mediated by SPP1
Shengpeng Zhang1, Fengge Zhang2, Limin Feng1
1Department of Obstetrics and Gynecology, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070 P.R. China.
Abstract:
Secreted protein acidic and rich in cysteines-like 1 (SPARCL1) is implicated in tumor progression and considered as a tumor suppressor. Aim of the study is to investigate the role of SPARCL1 in the regulation of tumor biology. SPARCL1 expression in human cervical cells was determined through western blot and RT-PCR. The effects of SPARCL1 overexpression on cell proliferation, migration and invasion were evaluated through CCK8 assay, colony formation assay, Wound healing assay and Transwell assay, respectively. The gain function of Secreted phosphor protein 1 (SPP1) was also evaluated in these cell functions. We observed that SPARCL1 expression at protein levels and transcription levels was lower in HeLa cells than that in Ect1/E6E7 cells. When SPARCL1 was overexpressed in HeLa cells, cell proliferation, migration and invasion were greatly repressed. Additionally, SPARCL1 overexpression markedly downregulated SPP1 expression at transcription levels. Mechanistical study revealed that SPP1 overexpression could greatly counteract the effects of SPARCL1 overexpression on the aforementioned cell processes and inhibit the phosphorylation of focal adhesion kinase (FAK) and extracellular regulated protein kinases (ERK). Our findings indicated that HeLa cells overexpressing SPARCL1 showed weaker abilities of proliferation, migration and invasion, and its effects could be neutralized by SPP1 overexpression possibly via FAK/ERK pathway. The relationship of SPARCL1 and SPP1 could help us to further understand the pathogenesis of cervical cancer and SPARCL1/SPP1 could be beneficial therapeutic targets in cervical cancer.
Insights
Secreted protein acidic and rich in cysteines-like 1 (SPARCL1) suppresses cervical cancer progression by inhibiting cell proliferation, migration, and invasion. Its effects are mediated through Secreted phosphor protein 1 (SPP1) and the FAK/ERK pathway.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Secreted protein acidic and rich in cysteines-like 1 (SPARCL1) is a known tumor suppressor involved in cancer progression.
- Understanding SPARCL1's role in cervical cancer is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the regulatory role of SPARCL1 in cervical tumor biology.
- To elucidate the relationship between SPARCL1 and Secreted phosphor protein 1 (SPP1) in cervical cancer cells.
Main Methods:
- Western blot and RT-PCR to assess SPARCL1 expression.
- Cell proliferation, migration, and invasion assays (CCK8, colony formation, wound healing, Transwell).
- Overexpression studies of SPARCL1 and SPP1, and analysis of FAK/ERK pathway phosphorylation.
Main Results:
- SPARCL1 expression was lower in HeLa cells compared to Ect1/E6E7 cells.
- SPARCL1 overexpression repressed proliferation, migration, and invasion in HeLa cells.
- SPARCL1 overexpression downregulated SPP1, and SPP1 overexpression counteracted SPARCL1's effects, inhibiting FAK/ERK phosphorylation.
Conclusions:
- SPARCL1 acts as a tumor suppressor in cervical cancer by inhibiting cell proliferation, migration, and invasion.
- SPP1 antagonizes SPARCL1's tumor-suppressive effects, potentially via the FAK/ERK pathway.
- SPARCL1 and SPP1 represent potential therapeutic targets for cervical cancer treatment.
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