Selective participation of c-Jun with Fra-2/c-Fos promotes aggressive tumor phenotypes and poor prognosis in tongue cancer

Gupta, Shilpi; Kumar, Prabhat; Kaur, Harsimrut; Sharma, Nitasha; Saluja, Daman; Bharti, Alok C.; Das, Bhudev C.

doi:10.1038/srep16811

Cited by 46 publications

(65 citation statements)

References 55 publications

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“…It is likely that presence of JunB and JunD that are participating in HPV transcription may out-compete c-Jun and dampen the aggressive behavior of HPV-positive tumors. Presence of c-Jun AP-1 complex was associated with aggressive HPV-negative tongue cancer [18]. Therefore, specific combinations of AP-1 members, as observed in this study, are not only productive for HPV transcription but may represent a cocktail that govern overall behavior of even HPV-negative tumors.…”

Section: Categorymentioning

confidence: 66%

Characterization of key transcription factors as molecular signatures of HPV‐positive and HPV‐negative oral cancers

et al. 2017

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Prior studies established constitutively active AP‐1, NF‐κB, and STAT3 signaling in oral cancer. Differential expression/activation of specific members of these transcription factors has been documented in HPV‐positive oral lesions that respond better to therapy. We performed a comprehensive analysis of differentially expressed, transcriptionally active members of these pivotal signaling mediators to develop specific signatures of HPV‐positive and HPV‐negative oral lesions by immunohistochemical method that is applicable in low‐resource settings. We examined a total of 31 prospective and 30 formalin‐fixed, paraffin‐embedded tissues from treatment‐naïve, histopathologically and clinically confirmed cases diagnosed as oral or oropharyngeal squamous cell carcinoma (OSCC/OPSCC). Following determination of their HPV status by GP5 + /GP6 + PCR, the sequential sections of the tissues were evaluated for expression of JunB, JunD, c‐Fos, p50, p65, STAT3, and pSTAT3(Y705), along with two key regulatory proteins pEGFR and p16 by IHC. Independent analysis of JunB and p65 showed direct correlation with HPV positivity, whereas STAT3 and pSTAT3 were inversely correlated. A combined analysis of transcription factors revealed a more restrictive combination, characterized by the presence of AP‐1 and NF‐κB lacking involvement of STAT3 that strongly correlated with HPV‐positive tumors. Presence of STAT3/pSTAT3 with NF‐κB irrespective of the presence or absence of AP‐1 members was present in HPV‐negative lesions. Expression of pSTAT3 strongly correlated with all the AP‐1/NF‐κB members (except JunD), its upstream activator pEGFRY 1092, and HPV infection‐related negative regulator p16. Overall, we show a simple combination of AP‐1, NF‐κB, and STAT3 members’ expression that may serve as molecular signature of HPV‐positive lesions or more broadly the tumors that show better prognosis.

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Section: Categorymentioning

confidence: 66%

Characterization of key transcription factors as molecular signatures of HPV‐positive and HPV‐negative oral cancers

et al. 2017

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“…Despite advanced surgical techniques in various combinations with radiation and chemotherapy, the overall 5‐year survival rate of HNSCC patients is <50% . Tongue squamous cell carcinoma (TSCC) is a common subtype of HNSCC, which is more biologically aggressive than other oral HNSCC cancers . Therapeutic target treatment for TSCC has not been currently met.…”

Section: Introductionmentioning

confidence: 99%

IRX5 promotes NF‐κB signalling to increase proliferation, migration and invasion via OPN in tongue squamous cell carcinoma

Huang

Song

Sun

et al. 2018

J Cellular Molecular Medi

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Iroquois homeobox gene 5 (Irx5) is a highly conserved member of the Iroquois homeobox gene family. Members of this family play distinct and overlapping roles in normal embryonic cell patterning and development of malignancies. In this study, we observed that IRX5 was abnormally abundant in tongue squamous cell carcinoma (TSCC) tissues and cell lines. We used gain‐ and loss‐of‐function methods to overexpress and knockdown IRX5 expression in the TSCC cell line CAL27. Our results elucidated that elevated levels of IRX5 promoted proliferation, migration and invasion of TSCC cells, whereas stable or transient knockdown of IRX5 expression suppressed TSCC cell proliferation, migration and invasion. As a transcription factor, IRX5 performed this function by targeting osteopontin (OPN) promoter and activating the NF‐κB pathway. Finally, studies in xenograft tumour model showed that IRX5 significantly enhanced OPN expression and promoted tumour growth. Taken together, our study elucidates a promotive effect of IRX5 in TSCC through the connection with OPN. These findings reveal the new molecular mechanism of TSCC, which may potentiate its use as a novel molecular therapy target for TSCC.

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“…It is involved in regulating cell cycle, cell growth, apoptosis, and cell division. Tumor suppressor gene p53 is a transcription factor that can directly or indirectly control the cell cycle genes or apoptosis-related gene expression, and is involved in the apoptosis-related death receptor pathway and mitochondrial pathway [18,19]. Wild-type p53 protein plays a negative role in regulating cell growth.…”

Section: Discussionmentioning

confidence: 99%

P53 and Murine Double Mimute 2 (MDM2) Expression Changes and Significance in Different Types of Endometrial Lesions

Jiang

Dan

et al. 2016

Med Sci Monit

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BackgroundEndometrial lesions are common in obstetrics and gynecology, including endometrial polyps, uterine adenomyosis, and malignant endometrial adenocarcinoma. Endometrial lesions seriously affect women’s health, fertility, quality of life, and life safety. As a pro-apoptosis gene, p53 is considered to be closely related with human tumors. Murine double mimute 2 (MDM2) is an oncogene that can promote tumor occurrence and development. P53 and MDM2 expression and significance in different types of endometrial lesions have not been fully elucidated.Material/MethodsNormal endometrium, endometrial polyps, uterine adenomyosis, and endometrial adenocarcinoma tissue samples were collected. Real-time PCR was used to detect p53 and MDM2 mRNA expression. Immunohistochemical staining and Western blot analysis were applied to test p53 and MDM2 protein expression. Their correlation with clinical staging of endometrial adenocarcinoma was analyzed.ResultsP53 and MDM2 mRNA and protein expression were significantly elevated in the endometrial polyps group and the endometrial adenocarcinoma group compared with the normal control group (P<0.05). Their levels increased more obviously in endometrial adenocarcinoma compared with endometrial polyps (P<0.05). P53 and MDM2 mRNA and protein expression were slightly enhanced in uterine adenomyosis compared with normal controls, but this difference lacked statistical significance (P>0.05). P53 and MDM2 mRNA and protein level showed a positive correlation. Significantly higher expression of p53 or MDM2 was observed in patients with stage III compared to those in patients with stage II. Higher expression was also observed in patients with stage II than in patients with stage I.ConclusionsP53 and MDM2 mRNA and protein were elevated in endometrial polyps and endometrial adenocarcinoma and their expressions were correlated with clinical staging of endometrial adenocarcinoma. They can promote cancer occurrence and development, and can be treated to assist diagnosis and provide a reference for treatment.

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Selective participation of c-Jun with Fra-2/c-Fos promotes aggressive tumor phenotypes and poor prognosis in tongue cancer

Cited by 46 publications

References 55 publications

Characterization of key transcription factors as molecular signatures of HPV‐positive and HPV‐negative oral cancers

Characterization of key transcription factors as molecular signatures of HPV‐positive and HPV‐negative oral cancers

IRX5 promotes NF‐κB signalling to increase proliferation, migration and invasion via OPN in tongue squamous cell carcinoma

P53 and Murine Double Mimute 2 (MDM2) Expression Changes and Significance in Different Types of Endometrial Lesions

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