EGFR‐mediated Akt and MAPKs signal pathways play a crucial role in patulin‐induced cell proliferation in primary murine keratinocytes via modulation of <i>Cyclin D1</i> and <i>COX‐2</i> expression

Alam, Shamshad; Pal, Anu; Kumar, Rahul; Dwivedi, Premendra D.; Das, Mukul; Ansari, Kausar M.

doi:10.1002/mc.22060

Cited by 20 publications

(15 citation statements)

References 54 publications

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“…We adopted a TargerScan database searching method search and IPA analysis to identify putative targets. Among them, we found EGFR, AKT2, and CCND1 were the top candidates and of particular interesting because they have shown their essential roles in many cancers and are crucial components in the same signaling pathway 36 37 38 39 . The target prediction programs predicted that miR-2861 had one seed region that matched the 3′UTR of human EGFR (position of 3′UTR: 421-428); five seed regions matched the 3′UTR of human AKT2 (position of 3′UTR: site 1: 133–139; site 2: 435–442; site 3: 990-995; site 4: 1791–1798; site 5:1993-1998); and one seed region matched the 3′UTR of human CCND1 (position of 3′UTR: 2831–2837) ( Fig.…”

Section: Resultsmentioning

confidence: 97%

miR-2861 acts as a tumor suppressor via targeting EGFR/AKT2/CCND1 pathway in cervical cancer induced by human papillomavirus virus 16 E6

Wan

Chen

et al. 2016

Sci Rep

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Persistent infection with oncogenic human papillomavirus viruses (HPVs) is a casual factor for cervical cancer and its precursors, and the abnormal constitutive expression of viral oncoprotein E6 is a key event during the malignant transformation. Here, we performed miRNA microarray to identify changes of miRNAs following ectopic HPV16 E6 overexpression in HEK293T cells and found miR-2861 was greatly decreased in both HEK293T and HaCaT cells expressing HPV16 E6 compared to vector control. Further, we demonstrated a biological link among HPV16 E6, miR-2861, EGFR, AKT2, and CCND1 in cervical cancer cells. We showed that miR-2861 was downregulated in cervical cancer tissues and negatively correlated with advanced tumor stage and lymph node metastasis. Overexpression of miR-2861 suppressed cervical cancer cell proliferation and invasion and enhanced apoptosis. Subsequent investigation revealed that EGFR, AKT2, and CCND1 were all the direct targets of miR-2861. Importantly, silencing EGFR, AKT2, and/or CCND1 recapitulated the cellular effects seen upon miR-2861 overexpression. Restoration of EGFR, AKT2, and/or CCND1 counteracted the effects of miR-2861 expression. Thus, we identified a new pathway employing miR-2861, EGFR, AKT2, and CCND1 that may mediate HPV16 E6 induced initiation and progression of cervical cancer.

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Section: Resultsmentioning

confidence: 97%

miR-2861 acts as a tumor suppressor via targeting EGFR/AKT2/CCND1 pathway in cervical cancer induced by human papillomavirus virus 16 E6

Wan

Chen

et al. 2016

Sci Rep

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“…Phosphorylated PI3K/AKT can promote cell growth and decrease apoptosis via increased Bcl-2/BAX ratio in human chondrosarcoma (CS) [ 40 ]. Cyclin D1 can be induced by growth factors through activation of various signaling pathways including PI3K/AKT, NF-kB [ 41 – 43 ], and p-AKT plays a crucial role in inducing cell proliferation by modulation of cyclin D1 in primary murine keratinocytes [ 43 , 44 ]. In the present study, PTEN expression was up- regulation when SALL4 was reduced by siRNA-SALL4, as a result, the inhibitory action of PTEN on PI3K/AKT signaling was weaken, thus receded the cycling D1 level which arrested the cell cycle at G1 phase, regulating glioma proliferation.…”

Section: Discussionmentioning

confidence: 99%

SALL4 suppresses PTEN expression to promote glioma cell proliferation via PI3K/AKT signaling pathway

Liu

et al. 2017

J Neurooncol

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Spalt-like transcription factor 4 (SALL4), a oncogene, is known to participate in multiple carcinomas, and is up-regulated in glioma. However, its actual role and underlying mechanisms in the development of glioma remain unclear. The present study explored the molecular functions of SALL4 in promoting cell proliferation in glioma. The expression level of SALL4 in 69 human glioma samples and six non-tumor brain tissues was determined using real-time polymerase chain reaction (PCR). Then, we transfected U87 and U251 cell lines with siRNA, and assessed cellular proliferation and cell cycle to understand the function of SALL4, and the relationship between SALL4, PTEN and PI3K/AKT pathway. PCR confirmed that the expression of SALL4 was higher in the glioma samples than non-tumor brain tissues. Cellular growth and proliferation were dramatically reduced following inhibition of SALL4 expression. Western blot showed increase in PTEN expression when SALL4 was silenced, which in turn depressed the activation of PI3K/AKT pathway, suggesting that PTEN was a downstream target of SALL4 in glioma development. Therefore, SALL4 could act as a proto-oncogene by regulating the PTEN/PI3K/AKT signaling pathway, thereby facilitating proliferation of glioma cells.

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“…Therefore, suppression of COX-2 expression has become an important target for the prevention and treatment of colon cancer [ 50 – 52 ]. EGFR-mediated MAPK signaling pathways are known to play a crucial role in cell proliferation via the modulation of COX-2 expression [ 53 ]. We found that the expression of COX-2 in colon cancer cells was significantly reduced by the combination treatment of cetuximab and cisplatin.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Inhibitory Effects of Cetuximab and Cisplatin on Human Colon Cancer Cell GrowthviaInhibition of the ERK-Dependent EGF Receptor Signaling Pathway

Son

Hong

Ban

et al. 2015

BioMed Research International

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The purpose of this study was to evaluate the anticancer efficacy of cetuximab combined with cisplatin (combination treatment) on colon cancer growth, as well as its underlying action mechanism. Combination treatment synergistically potentiated the effect of cetuximab on cell growth inhibition and apoptosis induction in HCT116 and SW480 cells. Combination treatment further suppressed the expression of the activated form of epidermal growth factor receptor (EGFR) and MAP kinase (p-ERK and p-p38) and also significantly inhibited the activity of activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). Additionally, the expression of cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) mRNA was significantly reduced by the combination treatment as compared to the expression seen for treatment with cetuximab or cisplatin alone. We found that the synergistic inhibitory effects of cetuximab and cisplatin on AP-1 and NF-κB activation, as well as on cell viability, were reversed by pretreatment with an ERK inhibitor. Results demonstrate that combined treatment with cetuximab and cisplatin exerts synergistic anticancer effects on colon cancer cells and also suggest that the ERK pathway plays a critical role in these effects via the suppression of the EGFR signaling pathway, along with the inhibition of COX-2, IL-8, and AP-1 and NF-κB.

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EGFR‐mediated Akt and MAPKs signal pathways play a crucial role in patulin‐induced cell proliferation in primary murine keratinocytes via modulation of Cyclin D1 and COX‐2 expression

Cited by 20 publications

References 54 publications

miR-2861 acts as a tumor suppressor via targeting EGFR/AKT2/CCND1 pathway in cervical cancer induced by human papillomavirus virus 16 E6

miR-2861 acts as a tumor suppressor via targeting EGFR/AKT2/CCND1 pathway in cervical cancer induced by human papillomavirus virus 16 E6

SALL4 suppresses PTEN expression to promote glioma cell proliferation via PI3K/AKT signaling pathway

Synergistic Inhibitory Effects of Cetuximab and Cisplatin on Human Colon Cancer Cell GrowthviaInhibition of the ERK-Dependent EGF Receptor Signaling Pathway

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