Down-regulation of IFITM1 and its growth inhibitory role in cervical squamous cell carcinoma

Weinan Zheng1,2, Zhimin Zhao1,2, Xinan Yi3

  • 1Department of Biochemistry and Molecular Biology, Department of Human Anatomy and Histology and Embryology, Basic Medical Science of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei China.

Cancer Cell International
|October 21, 2017
PubMed
Abstract

Insights

Interferon-induced transmembrane protein 1 (IFITM1) may suppress cervical cancer growth. Lower IFITM1 gene expression and higher promoter methylation were observed in cervical cancer tissues, suggesting a protective role.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Cervical cancer is a leading cause of mortality in women globally.
  • Interferon-induced transmembrane protein 1 (IFITM1) has known roles in antiviral defense, cell adhesion, and carcinogenesis.
  • The specific function of the IFITM1 gene in cervical squamous cell carcinoma remains largely uncharacterized.

Purpose of the Study:

  • To investigate the expression patterns of the IFITM1 gene in cervical squamous cell carcinoma.
  • To elucidate the functional role of IFITM1 in the proliferation, migration, and invasion of cervical cancer cells.

Main Methods:

  • Quantitative real-time RT-PCR and immunohistochemistry were used to assess IFITM1 mRNA and protein levels in tumor and adjacent normal tissues.
  • Methylation-specific PCR was employed to detect promoter methylation of the IFITM1 gene.
  • HeLa cells were transfected with an IFITM1 expression vector to evaluate its effects on cell proliferation, migration, invasion, and apoptosis.

Main Results:

  • IFITM1 protein expression was significantly different between chronic cervicitis and cervical carcinoma samples (P < 0.01).
  • IFITM1 mRNA levels were significantly lower in cervical cancer tissues compared to normal tissues (P < 0.05), alongside increased promoter methylation (P < 0.05).
  • Overexpression of IFITM1 in HeLa cells led to decreased cell migration and invasion, inhibited proliferation, and increased apoptosis.

Conclusions:

  • Reduced expression and increased promoter methylation of the IFITM1 gene are associated with cervical squamous cell carcinoma.
  • IFITM1 gene expression demonstrates a potential tumor-suppressive role by inhibiting proliferation, migration, and invasion in cervical cancer cells.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.3K
TGF - &#946; Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.7K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.9K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.6K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.9K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.1K