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Published on: October 27, 2014
TM7SF2 regulates cell proliferation and apoptosis by activation of C-Raf/ERK pathway in cervical cancer
Yichi Xu1, Xin Chen1, Shuya Pan1
1Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
Abstract:
Transmembrane 7 superfamily member 2 (TM7SF2) coding an enzyme involved in cholesterol metabolism has been found to be differentially expressed in kinds of tissues. Nevertheless, the role of TM7SF2 in the regulation of growth and progression among various cancers is unclear. In this study, the immunohistochemistry (IHC) assay, real-time RT-PCR and western blotting analysis were used to determine the TM7SF2 expression in cervical cancer tissues. Next, we used multiple methods to determine the ability of cell proliferation, migration, invasion, apoptosis, and cell cycle in cervical cancer cells after TM7SF2 modulation, such as CCK8 assay, colony formation assay, Transwell assay, wound healing assay, and flow cytometry. Our results revealed that upregulation of TM7SF2 facilitated cell proliferation and metastasis, suppressed cell apoptosis and prevented G0/G1 phase arrests in C33A and SiHa cells. Consistently, the opposite effects were observed after TM7SF2 knockout in cervical cancer cells. Further, we found that TM7SF2 participated in promoting tumorigenesis and progression via activation of C-Raf/ERK pathway in cervical cancer, which can be partly reversed by Raf inhibitor LY3009120. Moreover, TM7SF2 overexpression contributed to enhancement of xenograft tumor growth in vivo. Our findings indicated that TM7SF2 plays a vital role in tumor promotion by involving in C-Raf/ERK activation. Therefore, TM7SF2 could serve as a therapeutic target in future cervical cancer treatment.
Insights
Transmembrane 7 superfamily member 2 (TM7SF2) promotes cervical cancer growth and metastasis by activating the C-Raf/ERK pathway. Targeting TM7SF2 may offer a new therapeutic strategy for cervical cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Transmembrane 7 superfamily member 2 (TM7SF2) is involved in cholesterol metabolism and its role in cancer progression is largely unknown.
- Understanding TM7SF2's function in cervical cancer is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of TM7SF2 in the regulation of cervical cancer cell growth, proliferation, migration, invasion, and apoptosis.
- To elucidate the underlying molecular mechanisms, including the involvement of the C-Raf/ERK pathway.
Main Methods:
- Immunohistochemistry (IHC), real-time RT-PCR, and western blotting were used to assess TM7SF2 expression in cervical cancer tissues.
- In vitro assays (CCK8, colony formation, Transwell, wound healing, flow cytometry) evaluated cellular functions after TM7SF2 modulation.
- In vivo xenograft models assessed tumor growth.
Main Results:
- Upregulation of TM7SF2 enhanced cervical cancer cell proliferation, migration, and invasion while suppressing apoptosis.
- TM7SF2 knockout reversed these effects, indicating its oncogenic role.
- TM7SF2 overexpression promoted xenograft tumor growth and activated the C-Raf/ERK pathway.
Conclusions:
- TM7SF2 plays a significant role in promoting cervical cancer tumorigenesis and progression through C-Raf/ERK pathway activation.
- TM7SF2 represents a potential therapeutic target for cervical cancer treatment.
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