SM22α-induced activation of p16INK4a/retinoblastoma pathway promotes cellular senescence caused by a subclinical dose of γ-radiation and doxorubicin in HepG2 cells

Kim, Tae Rim; Lee, Hee Min; Lee, So Yong; Kim, Eun Jin; Kim, Kug Chan; Paik, Sang Gi; Cho, Eun Wie; Kim, In Gyu

doi:10.1016/j.bbrc.2010.08.018

Cited by 17 publications

(18 citation statements)

References 26 publications

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“…We also found that MT1G re-expression slightly inhibited phosphorylation of Rb in the present study, implicating the effect of MT1G on cell growth at least partially through modulating the activity of Rb/E2F pathway. This finding was supported by a recent study that SM22α overexpression activated the Rb/E2F pathway through elevating MT1G expression in human hepatocarcinoma cells [46]. …”

Section: Discussionsupporting

confidence: 70%

Metallothionein 1G functions as a tumor suppressor in thyroid cancer through modulating the PI3K/Akt signaling pathway

Guan

et al. 2013

BMC Cancer

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BackgroundMT1G inactivation mediated by promoter methylation has been reported in thyroid cancer. However, the role of MT1G in thyroid carcinogenesis remains unclear. The aim of this study is to examine the biological functions and related molecular mechanisms of MT1G in thyroid cancer.MethodsMethylation-specific PCR (MSP) was performed to analyze promoter methylation of MT1G and its relationship with clinicopathological characteristics of papillary thyroid cancer (PTC) patients. Conventional and real-time quantitative RT-PCR assays were used to evaluate mRNA expression. The functions of ectopic MT1G expression were determined by cell proliferation and colony formation, cell cycle and apoptosis, as well as cell migration and invasion assays.ResultsMT1G expression was frequently silenced or down-regulated in thyroid cancer cell lines, and was also significantly decreased in primary thyroid cancer tissues compared with non-malignant thyroid tissues. Promoter methylation, along with histone modification, contributes to MT1G inactivation in thyroid tumorigenesis. Moreover, our data showed that MT1G hypermethylation was significantly positively associated with lymph node metastasis in PTC patients. Importantly, restoring MT1G expression in thyroid cancer cells dramatically suppressed cell growth and invasiveness, and induced cell cycle arrest and apoptosis through inhibiting phosphorylation of Akt and Rb.ConclusionsWe have for the first time revealed that MT1G appears to be functional tumor suppressor involved in thyroid carcinogenesis mainly through modulating the phosphatidylinositol-3-kinase (PI3K)/Akt pathway and partially through regulating the activity of Rb/E2F pathway in this study.

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Section: Discussionsupporting

confidence: 70%

Metallothionein 1G functions as a tumor suppressor in thyroid cancer through modulating the PI3K/Akt signaling pathway

Guan

et al. 2013

BMC Cancer

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“…Chemo‐resistance of HepG2 cells is associated with cellular senescence induced by SM22α overexpression [11,12]. SM22α overexpression severely inhibited cell growth and activated the p16 INK4a /pRB senescence signaling pathway.…”

Section: Resultsmentioning

confidence: 99%

“…Cell death was measured by sub-G 1 /G 0 phase analysis of propidium iodide-stained cells using the Epics XL flow cytometer (Beckman Coulter Counter, Fullerton, CA, USA), as described previously [14]. Colony forming assay was performed as described previously [12].…”

Section: Measurement Of Cell Death and Colony Forming Assaymentioning

confidence: 99%

Hypoxia‐induced SM22α in A549 cells activates the IGF1R/PI3K/Akt pathway, conferring cellular resistance against chemo‐ and radiation therapy

et al. 2012

Self Cite

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a b s t r a c tChemo-or radiation-resistance in tumors caused by hypoxia often undermines efficacy of cancer therapy. Thus, therapies that overcome cellular resistance during hypoxia are necessary. SM22a is an actin-binding protein found in smooth muscle, fibroblasts, and some epithelium. We demonstrate that SM22a is induced in A549 non-small cell lung carcinoma cells by hypoxia and its overexpression increased chemo-and radiation-resistance. Hypoxia-mediated induction of SM22a expression is hypoxia-inducible factor-independent. Moreover, SM22a overexpression enhances tumor cell growth and activates the IGF1R/PI3K/Akt pathway via direct interaction with IGF1Rb. Our results suggest SM22a as a novel regulator of hypoxic survival pathway of A549 NSCLC cells. Structured summary of protein interactions:IGFR1 Beta physically interacts with SM22 alpha by anti bait coimmunoprecipitation (View Interaction: 1, 2)

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“…We have also shown that the complete blockade of ERN1 signal transduction pathway leads to the induction of the expression of several genes which encode for retinoblastoma binding and associate proteins (EID1, JARID1B, RBAP48 and DNA endonuclease CTIP) that bind directly to retinoblastoma proteins to regulate cell proliferation, apoptosis, and tumor growth via retinoblastoma suppressor pathways [15,23,24]. These results also agree with anti-tumor effects of the complete blockade of ERN1 signaling pathway as well as with biological functions of the studied proteins [13,14,25].…”

Section: Discussionmentioning

confidence: 99%

“…There is data that retinoblastoma controls nuclear receptor networks critical for tumor progression and that it does so via E2F transcription factor 1-mediated regulation of androgen receptor expression and output [23]. Moreover, the p16(INK4a)/ retinoblastoma pathway participates in the regulation of cellular senescence caused by damaging agents [24]. The protein encoded by retinoblastoma like 1 (RBL1) gene is similar in sequence and possibly function to the product of the RB1 gene.…”

Section: Introductionmentioning

confidence: 99%

Effect of hypoxia and glutamine or glucose deprivation on the expression of retinoblastoma and retinoblastoma-related genes in ERN1 knockdown glioma U87 cell line

Minchenko¹,

Karbovskyi²,

Danilovskyi³

et al. 2012

AJMB

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The expression of retinoblastoma and several retinoblastoma-related genes was studied in glioma cell line U87 and its subline with knockdown of ERN1 (endoplasmic reticulum-nuclei-1), the main endoplasmic reticulum stress sensing and signaling enzyme. It was shown that a blockade of the ERN1 enzyme function increases the expression levels of retinoblastoma, retinoblastoma-like 1 and most retinoblastoma related genes: EID1, JARID1B, E2F1, E2F3, RBAP48 and CTIP, does not change RNF40 and RBAP46 and decreases KDM5A. We have also demonstrated that hypoxia reduces the expression levels of retinoblastoma, EID1, and E2F1 in ERN1-deficient glioma cells only. At the same time, the expression levels of retinoblastoma-like 1, E2F3, RBAP46, RBAP48 and CTIP decrease, while JARID1B and RBBP2 increase in both types of cells in hypoxic conditions, but the expression is much stronger in cells with suppressed function of ERN1. The expression level of JARID1B and KDM-5A mRNA is also enhanced in glutamine deprivation condition in both tested cell types, moreover, this effect is amplified by the blockade of the ERN1 enzyme function. The expression levels of retinoblastoma, EID1, RBAP48, and E2F3 are decreased in glutamine deprivation condition only in ERN1-deficient glioma cells, but RBL1, CTIP, RBAP46, and E2F1-in both tested cell types with more significant effect in ERN1-deficient cells. Glucose deprivation condition leads to a decrease of expression levels of retinoblastoma, RBL1, E2F3, RBAP46, and RBAP48 in both used cell types and of EID1 and E2F1 only in glioma cells with suppressed function of signaling enzyme ERN1. Thus, expression levels of retinoblastoma and most retinoblastoma-related genes are increased under a blockade of ERN1 enzyme function and significantly changed in hypoxia, glucose or glutamine deprivation conditions both in control U87 cells and ERN1-deficient cells, but inhibition of the unfolded protein response sensor ERN1 predominantly enhances these effects. Moreover, it is possible that the induction of the expression of retinoblastoma and most retinoblastomarelated genes after knockdown of ERN1 plays an important role in suppression of glioma proliferation.

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SM22α-induced activation of p16INK4a/retinoblastoma pathway promotes cellular senescence caused by a subclinical dose of γ-radiation and doxorubicin in HepG2 cells

Cited by 17 publications

References 26 publications

Metallothionein 1G functions as a tumor suppressor in thyroid cancer through modulating the PI3K/Akt signaling pathway

Metallothionein 1G functions as a tumor suppressor in thyroid cancer through modulating the PI3K/Akt signaling pathway

Hypoxia‐induced SM22α in A549 cells activates the IGF1R/PI3K/Akt pathway, conferring cellular resistance against chemo‐ and radiation therapy

Effect of hypoxia and glutamine or glucose deprivation on the expression of retinoblastoma and retinoblastoma-related genes in ERN1 knockdown glioma U87 cell line

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