Decreased expression of <i>FOXF2</i> as new predictor of poor prognosis in stage I non-small cell lung cancer

Kong, Ping; Li, Guangming; Tian, Yin; Song, Bin; Shi, Ruyi

doi:10.18632/oncotarget.10876

Cited by 18 publications

(28 citation statements)

References 41 publications

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“…FOXF2 exhibits inhibitory effects in most tumours. In lung cancer (except for non-small cell lung cancer 20,21 ) and RMS in mice 35 , FOXF2 mainly shows a promotive effect. In HCC 23 and breast cancer 18,19 , the effect of FOXF2 can be to inhibit and to promote.…”

Section: General Descriptionmentioning

confidence: 99%

“…Multiple studies have shown that FOXF2 can have roles in breast cancer 18,19 , lung cancer [20][21][22] , hepatocellular carcinoma (HCC) [23][24][25] , colorectal cancer (CRC) [26][27][28][29] , prostate cancer (PC) [30][31][32] , gastric cancer (GC) 33 , ovarian cancer (OC) 34 , rhabdomyosarcoma (RMS) in mice 35 and other tumours (Table 1). However, FOXF2 can both promote and inhibit proliferation, invasion and metastasis in tumours, depending on the type or subtype of the tumour.…”

Section: Introductionmentioning

confidence: 99%

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FOXF2 acts as a crucial molecule in tumours and embryonic development

Kang

Zhu

et al. 2020

Cell Death Dis

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As a key member of the forkhead box transcription factors, forkhead box F2 (FOXF2) serves as a transcriptional regulator and regulates downstream gene expression in embryonic development, metabolism and in some common diseases, such as stroke and gastroparesis. Recent studies have shown that aberrant expression of FOXF2 is associated with a variety of tumorigenic processes, such as proliferation, invasion and metastasis. The role of FOXF2 in the development of many different organs has been confirmed by studies and has been speculated about in case reports. We focus on the mechanisms and signal pathways of tumour development initiated by aberrant expression of FOXF2, and we summarize the diseases and signal pathways caused by aberrant expression of FOXF2 in embryogenesis. This article highlights the differences in the role of FOXF2 in different tumours and demonstrates that multiple factors can regulate FOXF2 levels. In addition, FOXF2 is considered a biomarker for the diagnosis or prognosis of various tumours. Therefore, regulating the level of FOXF2 is an ideal treatment for tumours. FOXF2 could also affect the expression of some organ-specific genes to modulate organogenesis and could serve as a biomarker for specific differentiated cells. Finally, we present prospects for the continued research focus of FOXF2. Facts FOXF2 exhibits inhibitory effects in most tumours. In lung cancer (except for non-small cell lung cancer) and rhabdomyosarcoma in mice, FOXF2 mainly shows a promotive effect. FOXF2 can both inhibit and promote HCC and breast cancer. Regulating the expression level of FOXF2 is an ideal treatment for tumours. Mutations in or deletions of FOXF2 occur in some patients with craniofacial deformities. Mice with suppressed FOXF2 expression show defective organogenesis, such as aglossia, eye deformity, cleft palate and intracranial haemorrhage. Open questions Does FOXF2 have a common mechanism in tumours? What signalling pathways and gene expression does FOXF2 affect in the development of different organs? Are there any specific mechanisms or proteins that can be targeted in the treatment of a FOXF2-affected diseases?

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Section: General Descriptionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

FOXF2 acts as a crucial molecule in tumours and embryonic development

Kang

Zhu

et al. 2020

Cell Death Dis

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“…FOXF2 was found to be associated with the development of multiple tumors. Kong et al [ 6 ] demonstrated that FOXF2 was a new independent predictive factor of non-small cell lung cancer. Its lower expression could lead to poor prognosis of patients, especially for patients with stage I non-small cell lung cancer.…”

Section: Introductionmentioning

confidence: 99%

FOXF2 inhibits proliferation, migration, and invasion of Hela cells by regulating Wnt signaling pathway

Zhang

Sang

et al. 2018

Bioscience Reports

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This article was aimed to study the FOXF2 effects on cervical cancer. Tumor tissues and adjacent tissues of 41 cervical cancer patients were collected. Human endometrial epithelial cells (hEEC) and Hela cells were cultured. FOXF2 expression vector and its empty vector were transfected into Hela cells, and named as pcDNA 3.1-FOXF2 group and Vector group, respectively. Hela cells without any treatment were set as Blank group. qRT-PCR was used to detect mRNA expression. Nude mouse xenograft assay was performed to test Hela cells proliferation ability in vivo. FOXF2 and β-catenin positive cell numbers were detected by immunohistochemistry. Protein expression was analyzed by Western blot. Cells migration and invasion were conducted by Transwell. Tumor tissues and Hela cells FOXF2 expression were lower than that in adjacent tissues and hEEC (P<0.01). Low FOXF2 expression predicted poor outcomes of cervical cancer patients. Compared with Blank group and Vector group, Hela cells of pcDNA 3.1-FOXF2 group were with higher FOXF2 expression, lower OD495 value, migrated and invaded cells, higher E-cadherin expression, lower Vimentin and Snail expression, smaller tumor volume in nude mice, lower c-Myc, CyclinDl, MMP9, Lgr5, and nuclear β-catenin expression (all P<0.01). FOXF2 inhibits Hela cells proliferation, migration, and invasion through regulating Wnt signaling pathway.

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“…In epithelial cells, these transcriptional factors are directly involved in the expression of cyclin dependent kinase inhibitors and CDKN2A gene under the control of TGFβ [ 46 , 47 ]. Both downregulation of anti-apoptotic targets as well as activation of proliferative metabolism have been observed as mechanisms contributing to MAPKi-R. Downregulation of FOXF2 has been shown to promote cancer progression, EMT, and metastatic invasion [ 48 ]. In contrast, a different member of the FOX family, the stem cell transcription factor forkhead box D3 (FOXD3) has been identified as an adaptive mediator of the response to MAPK pathway inhibition selectively in mutant BRAF melanomas [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Systems biology analysis of mitogen activated protein kinase inhibitor resistance in malignant melanoma

et al. 2018

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Background Kinase inhibition in the mitogen activated protein kinase (MAPK) pathway is a standard therapy for cancer patients with activating BRAF mutations. However, the anti-tumorigenic effect and clinical benefit are only transient, and tumors are prone to treatment resistance and relapse. To elucidate mechanistic insights into drug resistance, we have established an in vitro cellular model of MAPK inhibitor resistance in malignant melanoma. Methods The cellular model evolved in response to clinical dosage of the BRAF inhibitor, vemurafenib, PLX4032. We conducted transcriptomic expression profiling using RNA-Seq and RT-qPCR arrays. Pathways of melanogenesis, MAPK signaling, cell cycle, and metabolism were significantly enriched among the set of differentially expressed genes of vemurafenib-resistant cells vs control. The underlying mechanism of treatment resistance and pathway rewiring was uncovered to be based on non-genomic adaptation and validated in two distinct melanoma models, SK-MEL-28 and A375. Both cell lines have activating BRAF mutations and display metastatic potential. Results Downregulation of dual specific phosphatases, tumor suppressors, and negative MAPK regulators reengages mitogenic signaling. Upregulation of growth factors, cytokines, and cognate receptors triggers signaling pathways circumventing BRAF blockage. Further, changes in amino acid and one-carbon metabolism support cellular proliferation despite MAPK inhibitor treatment. In addition, treatment-resistant cells upregulate pigmentation and melanogenesis, pathways which partially overlap with MAPK signaling. Upstream regulator analysis discovered significant perturbation in oncogenic forkhead box and hypoxia inducible factor family transcription factors. Conclusions The established cellular models offer mechanistic insight into cellular changes and therapeutic targets under inhibitor resistance in malignant melanoma. At a systems biology level, the MAPK pathway undergoes major rewiring while acquiring inhibitor resistance. The outcome of this transcriptional plasticity is selection for a set of transcriptional master regulators, which circumvent upstream targeted kinases and provide alternative routes of mitogenic activation. A fine-woven network of redundant signals maintains similar effector genes allowing for tumor cell ...

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Decreased expression of FOXF2 as new predictor of poor prognosis in stage I non-small cell lung cancer

Cited by 18 publications

References 41 publications

FOXF2 acts as a crucial molecule in tumours and embryonic development

FOXF2 acts as a crucial molecule in tumours and embryonic development

FOXF2 inhibits proliferation, migration, and invasion of Hela cells by regulating Wnt signaling pathway

Systems biology analysis of mitogen activated protein kinase inhibitor resistance in malignant melanoma

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