Fra-1 is downregulated in cervical cancer tissues and promotes cervical cancer cell apoptosis by p53 signaling pathway in vitro

Xiao, Songshu; Zhou, Yanhong; Yi, Wei; Luo, Guijuan; Jiang, Bin; Tian, Qiang; Li, Yueran; Xue, Min

doi:10.3892/ijo.2015.2873

Cited by 41 publications

(33 citation statements)

References 45 publications

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“…It has also been demonstrated that upregulation of Fra-1 leads to chemosensitization of breast cancer stem cells 53 . In contrast, a recent study shows Fra-1 downregulation in cervical cancer and it promotes apoptosis 54 . Further, Fra-1 through a positive feedback loop via miR-134 & SDS22 amplifies ERK and JNK signaling and reduce chemosensitivity in ovarian cancer cells 55 .…”

Section: Discussionmentioning

confidence: 73%

Cervical cancer stem cells manifest radioresistance: Association with upregulated AP-1 activity

Tyagi

Vishnoi

Kaur

et al. 2017

Sci Rep

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Transcription factor AP-1 plays a central role in HPV-mediated cervical carcinogenesis. AP-1 has also been implicated in chemo-radio-resistance but the mechanism(s) remained unexplored. In the present study, cervical cancer stem-like cells (CaCxSLCs) isolated and enriched from cervical cancer cell lines SiHa and C33a demonstrated an elevated AP-1 DNA-binding activity in comparison to non-stem cervical cancer cells. Upon UV-irradiation, CaCxSLCs showed a UV exposure duration-dependent higher proliferation and highly increased AP-1 activity whereas it was completely abolished in non-stem cancer cells. CaCxSLCs also showed differential overexpression of c-Fos and c-Jun at transcript as well as in protein level. The loss of AP-1 activity and expression was accompanied by decrease in cell viability and proliferation in UV-irradiated non-stem cancer cells. Interestingly, CaCxSLCs treated with curcumin prior to UV-irradiation abolished AP-1 activity and a concomitant reduction in SP cells leading to abrogation of sphere forming ability, loss of proliferation, induction of apoptosis and the cells were poorly tumorigenic. The curcumin pre-treatment abolished the expression of c-Fos and c-Jun but upregulated Fra-1 expression in UV-irradiated CaCxSLCs. Thus, the study suggests a critical role of AP-1 protein in the manifestation of radioresistance but targeting with curcumin helps in radiosensitizing CaCxSLCs through upregulation of Fra-1.

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Section: Discussionmentioning

confidence: 73%

Cervical cancer stem cells manifest radioresistance: Association with upregulated AP-1 activity

Tyagi

Vishnoi

Kaur

et al. 2017

Sci Rep

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“…The expression of mRNA was assessed by evaluated threshold cycle (CT) values. The CT values were normalized with the expression levels of GAPDH and the relative amount of mRNA specific to each of the target genes was calculated using the 2 -ΔΔCT method (4,(18)(19)(20)(21). qPCR was done with the Bio-Rad CFK96™ Real-Time System (Bio-Rad Laboratories, Hercules, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Fra-1 can positively regulate transcription. Fra-1 activity is regulated transcriptionally as well as post-translationally (3,4). FRA-1 has been implicated in the development of airway squamous metaplasia and is frequently overexpressed in squamous cell carcinomas of the stomach and esophagus (2).…”

Section: Introductionmentioning

confidence: 99%

Fra-1 is upregulated in gastric cancer tissues and affects the PI3K/Akt and p53 signaling pathway in gastric cancer

Zhu

Gao

et al. 2015

International Journal of Oncology

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Gastric cancer is an aggressive disease that continues to have a daunting impact on global health. Fra-1 (FOSL1) plays important roles in oncogenesis in various malignancies. We investigated the expression of Fra-1 in gastric cancer (GC) tissues by qPCR, immunohistochemistry (IHC) and western blot technologies. The results showed that Fra-1 was overexpressed in gastric cancer tissues compared with the adjacent non‑cancerous tissues. To explore the possible mechanism of Fra-1 in GC, we elucidated the effect of Fra-1 in the apoptosis and cell cycle of gastric cancer cells, AGS, and found that a considerable decrease in apoptotic cells and increase of S phase rate were observed for AGS cells with Fra-1 overexpession. We identified and confirmed that Fra-1 affected the expression level of CTTN and EZR in vitro through LC-MS/MS analyses and western blot technology. Furthermore, we found that Fra-1 was correlated with dysregulation PI3K/Akt and p53 signaling pathway in gastric cancer tissues in vitro. Moreover, we found that Fra-1 overexpression affected the expression of PI3K, Akt, MDM2 and p53 in vivo. In summary, our results suggest that Fra-1 is upregulated in gastric cancer tissues and plays its function by affecting the PI3K/Akt and p53 signaling pathway in gastric cancer.

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“…Numerous proteins, including cluster of differentiation (CD)44, CD24, CD38, Fos-related antigen-1, heat shock protein β-1 and transcription factor SOX-9, have been implicated in cervical cancer, and dysregulation of these proteins is closely associated with the occurrence and outcome of cervical cancer (34)(35)(36)(37)(38)(39). However, the etiology of cervical carcinoma remains elusive.…”

Section: Discussionmentioning

confidence: 99%

TNFAIP8 promotes cisplatin resistance in cervical carcinoma cells by inhibiting cellular apoptosis

Su-xia

et al. 2019

Oncol Lett

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Cervical cancer is the second most prevalent malignant tumor in women worldwide. Failure of successful treatment is most prevalent in patients with the metastatic disease and the chemotherapy refractory disease. Tumor necrosis factor α-induced protein 8 (TNFAIP8) serves as an anti-apoptotic and pro-oncogenic protein, and is associated with cancer progression and poor prognosis in a number of different cancer types. However, the physiological and pathophysiological roles of TNFAIP8 in cervical carcinogenesis and development remain poorly understood. In the present study, it was demonstrated that TNFAIP8 protein expression levels were significantly increased in cervical cancer tissues compared with the non-tumor adjacent tissues using immunohistochemistry. Additionally, it was demonstrated that TNFAIP8 overexpression is associated with cisplatin resistance. Furthermore, depletion of TNFAIP8 impaired HeLa cell proliferation and viability in vitro, improved cisplatin sensitivity, and promoted cisplatin-induced cellular apoptosis and death. Subsequent mechanistic analysis demonstrated that TNFAIP8 silencing promoted caspase-8/-3 activation and p38 phosphorylation in HeLa cells treated with cisplatin, whereas apoptosis regulator B-cell lymphoma-2 expression was inhibited with TNFAIP8-silenced HeLa cells following treatment with cisplatin. These data suggested that TNFAIP8 serves as an anti-apoptotic protein against cisplatin-induced cell death, which eventually leads to chemotherapeutic drug-treatment failure. Therefore, the present data suggested that TNFAIP8 may be a promising therapeutic target for the treatment of cervical cancer.Abbreviations: TNFAIP8, tumor necrosis factor α-induced protein 8; MAPK, mitogen-activated protein kinase; CDDP, Cis-diamminedichloroplatinum

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Fra-1 is downregulated in cervical cancer tissues and promotes cervical cancer cell apoptosis by p53 signaling pathway in vitro

Cited by 41 publications

References 45 publications

Cervical cancer stem cells manifest radioresistance: Association with upregulated AP-1 activity

Cervical cancer stem cells manifest radioresistance: Association with upregulated AP-1 activity

Fra-1 is upregulated in gastric cancer tissues and affects the PI3K/Akt and p53 signaling pathway in gastric cancer

TNFAIP8 promotes cisplatin resistance in cervical carcinoma cells by inhibiting cellular apoptosis

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