Expression of Transcription Factor FOXC2 in Cervical Cancer and Effects of Silencing on Cervical Cancer Cell Proliferation

Zheng, Chunhua; Yuan, Quan; Li, Yi-Yang; Deng, Weiguo; Shao, Wang; Fu, Yan

doi:10.7314/apjcp.2014.15.4.1589

Cited by 16 publications

(8 citation statements)

References 22 publications

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“…Secondly, CSCs have the unique ability to divide either asymmetrically or symmetrically and, therefore, the control of mitosis will influence the proportion of CSCs within a tumour 56 57 58 . Although FOXC2 was previously shown to promote the proliferation of several cancer cell types 30 31 32 33 34 35 , we show here, for the first time, that FOXC2 regulates the G2/M transition of CSC-enriched TNBC cells and immortalized cells that have undergone EMT. Mechanistically how FOXC2 enhances mitotic entry remains unclear, but we found a tight correlation between FOXC2 and mitotic kinase CDK1 expression.…”

Section: Discussioncontrasting

confidence: 46%

“…The patient datasets analysed were previously described 34 . All gene expression microarrays of diagnosed breast cancer were profiled (U133A Gene Chip; Affymetrix, Santa Clara, California) in the Translational Molecular Pathology Department at the MD Anderson Cancer Centre, Houston, Texas.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, it was shown that only wild-type FOXC2, but not a phosphorylation-deficient mutant, was able to induce the expression of several cell cycle regulators, including cyclin-dependent kinase 1 (CDK1), suggesting a role for FOXC2 phosphorylation in the expression of cell cycle-specific genes 29 . Moreover, FOXC2 expression has been shown to enhance proliferation in several types of tumour cells 30 31 32 33 34 35 . Collectively, these studies indirectly link FOXC2 to the regulation of cell cycle and proliferation, although its role in the cell cycle of CSCs remains unclear.…”

mentioning

confidence: 99%

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FOXC2 regulates the G2/M transition of stem cell-rich breast cancer cells and sensitizes them to PLK1 inhibition

Pietilä

Vijay

Soundararajan

et al. 2016

Sci Rep

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Cancer cells with stem cell properties (CSCs) underpin the chemotherapy resistance and high therapeutic failure of triple-negative breast cancers (TNBCs). Even though CSCs are known to proliferate more slowly, they are sensitive to inhibitors of G2/M kinases such as polo-like kinase 1 (PLK1). Understanding the cell cycle regulatory mechanisms of CSCs will help target these cells more efficiently. Herein, we identify a novel role for the transcription factor FOXC2, which is mostly expressed in CSCs, in the regulation of cell cycle of CSC-enriched breast cancer cells. We demonstrate that FOXC2 expression is regulated in a cell cycle-dependent manner, with FOXC2 protein levels accumulating in G2, and rapidly decreasing during mitosis. Knockdown of FOXC2 in CSC-enriched TNBC cells delays mitotic entry without significantly affecting the overall proliferation rate of these cells. Moreover, PLK1 activity is important for FOXC2 protein stability, since PLK1 inhibition reduces FOXC2 protein levels. Indeed, FOXC2 expressing CSC-enriched TNBC cells are sensitive to PLK1 inhibition. Collectively, our findings demonstrate a novel role for FOXC2 as a regulator of the G2/M transition and elucidate the reason for the observed sensitivity of CSC-enriched breast cancer cells to PLK1 inhibitor.

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Section: Discussioncontrasting

confidence: 46%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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FOXC2 regulates the G2/M transition of stem cell-rich breast cancer cells and sensitizes them to PLK1 inhibition

Pietilä

Vijay

Soundararajan

et al. 2016

Sci Rep

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“…FOXC2, an important member of FOX family, has been reported to be overexpressed in a variety of human cancer, including colorectal cancer, esophageal cancer, gastric cancer, and so on [42][43][44]. The overexpression of FOXC2 has been found to be correlated with poor prognosis of patients and promotes proliferation, EMT and metastasis of tumor cells [45,46]. Previously, we have shown that FOXC2 could promote the CDDP resistant of ovarian cancer cells by reduction of CDDP-inducing apoptosis [16].…”

Section: Discussionmentioning

confidence: 99%

Forkhead Box Protein C2 Promotes Epithelial-Mesenchymal Transition, Migration and Invasion in Cisplatin-Resistant Human Ovarian Cancer Cell Line (SKOV3/CDDP)

Ding

Tian

et al. 2016

Cell Physiol Biochem

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Background/Aims: Forkhead Box Protein C2 (FOXC2) has been reported to be overexpressed in a variety of human cancers. However, it is unclear whether FOXC2 regulates epithelial-mesenchymal transition (EMT) in CDDP-resistant ovarian cancer cells. The aim of this study is to investigate the effects of FOXC2 on EMT and invasive characteristics of CDDP-resistant ovarian cancer cells and the underlying molecular mechanism. Methods: MTT, Western blot, scratch wound healing, matrigel transwell invasion, attachment and detachment assays were performed to detect half maximal inhibitory concentration (IC₅₀) of CDDP, expression of EMT-related proteins and invasive characteristics in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP) and its parental cell line (SKOV3). Small hairpin RNA (shRNA) was used to knockdown FOXC2 and analyze the effect of FOXC2 knockdown on EMT and invasive characteristics of SKOV3/CDDP cells. Also, the effect of FOXC2 upregulation on EMT and invasive characteristics of SKOV3 cells was analyzed. Furthermore, the molecular mechanism underlying FOXC2-regulating EMT in ovarian cancer cells was determined. Results: Compared with parental SKOV3 cell line, SKOV3/CDDP showed higher IC₅₀ of CDDP (43.26μM) (P<0.01) and acquired EMT phenotype and invasive characteristics. Gain- and loss-of-function assays indicated that shRNA-mediated FOXC2 knockdown could reverse EMT and reduce the capacity of migration, invasion, attachment and detachment in SKOV3/CDDP cell line and upregulation of FOXC2 could induce the reverse effects in parental SKOV3 cell line. Furthermore, it was found that activation of ERK or AKT/GSK-3β signaling pathways was involved in FOXC2-promoting EMT in CDDP-resistant ovarian cancer cells. Conclusions: Taken together, these data demonstrate that FOXC2 may be a promoter of EMT phenotype in CDDP-resistant ovarian cancer cells and a potential therapeutic target for the treatment of advanced ovarian cancer.

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“…FOXC2 acts as regulators of Lymphangiogenesis and Angiogenesis in Oral Squamous Cell Carcinoma (Sasahira et al, 2014). The expression of FOXC2 gene also increases with malignancy of Cervical Cancer, especially with blood vessel hyperplasia and invasion degree (Zheng et al, 2014). FOXL1 plays an inhibitory role in renal tumor progression and over-expression of FOXL1 can inhibit tumor cell growth, migration and invasion in renal cancer cells (Yang et al, 2013).…”

Section: 10475 Comprehensive Expression Analysis Suggests Functionalmentioning

confidence: 99%

Comprehensive Expression Analysis Suggests Functional Overlapping of Human FOX Transcription Factors in Cancer

Zhang¹,

FengTing²,

Zhang³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Forkhead-box (FOX) transcription factors comprise a large gene family that contains more than 50 members in man. Extensive studies have revealed that they not only have functions in control of growth and development, but also play important roles in different diseases, especially in cancer. However, biological functions for most of the members in the FOX family remain unknown. In the present study, the expression of 39 FOX genes in 48 kinds of cancer was mined from the Gene Expression Atlas database of European Bioinformatics Institute. The analysis results showed that some FOX genes demonstrate overlapping expression in various cancers, which suggests particular biological functions. The pleiotropic features of the FOX genes make them excellent candidates in efforts aimed to give medical treatment for cancers at the genetic level. The results also indicated that different FOX genes may have the synergy or antagonistics effects in the same cancers. The study provides clues for further functional analysis of FOX genes, especially for the pleiotropic biological functions and crosstalk of FOX genes in human cancers.

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Expression of Transcription Factor FOXC2 in Cervical Cancer and Effects of Silencing on Cervical Cancer Cell Proliferation

Cited by 16 publications

References 22 publications

FOXC2 regulates the G2/M transition of stem cell-rich breast cancer cells and sensitizes them to PLK1 inhibition

FOXC2 regulates the G2/M transition of stem cell-rich breast cancer cells and sensitizes them to PLK1 inhibition

Forkhead Box Protein C2 Promotes Epithelial-Mesenchymal Transition, Migration and Invasion in Cisplatin-Resistant Human Ovarian Cancer Cell Line (SKOV3/CDDP)

Comprehensive Expression Analysis Suggests Functional Overlapping of Human FOX Transcription Factors in Cancer

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