scholarly journals HP1γ Sensitizes Cervical Cancer Cells to Cisplatin through the Suppression of UBE2L3

2020 ◽  
Vol 21 (17) ◽  
pp. 5976 ◽  
Author(s):  
Sang Ah Yi ◽  
Go Woon Kim ◽  
Jung Yoo ◽  
Jeung-Whan Han ◽  
So Hee Kwon
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Nuclear Export ◽  
Nuclear Translocation ◽  
Leptomycin B ◽  
P53 Signaling ◽  
Cervical Cancer Cells ◽  
Ubiquitin Conjugating Enzyme ◽  
The Stability

Cisplatin is the most frequently used agent for chemotherapy against cervical cancer. However, recurrent use of cisplatin induces resistance, representing a major hurdle in the treatment of cervical cancer. Our previous study revealed that HP1γ suppresses UBE2L3, an E2 ubiquitin conjugating enzyme, thereby enhancing the stability of tumor suppressor p53 specifically in cervical cancer cells. As a follow-up study of our previous findings, here we have identified that the pharmacological substances, leptomycin B and doxorubicin, can improve the sensitivity of cervical cancer cells to cisplatin inducing HP1γ-mediated elevation of p53. Leptomycin B, which inhibits the nuclear export of HP1γ, increased cisplatin-dependent apoptosis induction by promoting the activation of p53 signaling. We also found that doxorubicin, which induces the DNA damage response, promotes HP1γ-mediated silencing of UBE2L3 and increases p53 stability. These effects resulted from the nuclear translocation and binding of HP1γ on the UBE2L3 promoter. Doxorubicin sensitized the cisplatin-resistant cervical cancer cells, enhancing their p53 levels and rate of apoptosis when administered together with cisplatin. Our findings reveal a therapeutic strategy to target a specific molecular pathway that contributes to p53 degradation for the treatment of patients with cervical cancer, particularly with cisplatin resistance.

Dominant negative Ubiquitin-conjugating enzyme E2C sensitizes cervical cancer cells to radiation

2012 ◽  
Vol 88 (9) ◽  
pp. 629-634 ◽  
Author(s):  
Mayil Vahanan Bose ◽  
Gopisetty Gopal ◽  
Ganesharaja Selvaluxmy ◽  
Thangarajan Rajkumar
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Dominant Negative ◽  
Cervical Cancer Cells ◽  
Ubiquitin Conjugating Enzyme ◽  
Conjugating Enzyme

scholarly journals VERU-111 suppresses tumor growth and metastatic phenotypes of cervical cancer cells through the activation of p53 signaling pathway

2020 ◽  
Vol 470 ◽  
pp. 64-74 ◽  
Author(s):  
Vivek K. Kashyap ◽  
Nirnoy Dan ◽  
Neeraj Chauhan ◽  
Qinghui Wang ◽  
Saini Setua ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
P53 Signaling ◽  
Cervical Cancer Cells ◽  
P53 Signaling Pathway

scholarly journals Ubiquitin-conjugating enzyme E2T promotes tumor stem cell characteristics and migration of cervical cancer cells by regulating the GRP78/FAK pathway

2021 ◽  
Vol 16 (1) ◽  
pp. 1082-1090
Author(s):  
YanMei Liu ◽  
WenLi Ji ◽  
Na Yue ◽  
Weidong Zhou
Keyword(s):  
Cervical Cancer ◽  
Stem Cell ◽  
Protein Expression ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Self Renewal ◽  
Cervical Cancer Cells ◽  
Ubiquitin Conjugating Enzyme ◽  
And Migration ◽  
Conjugating Enzyme

Abstract Ubiquitin-conjugating enzyme E2T (UBE2T) functions as an E2 ubiquitin-conjugating enzyme in the ubiquitin-proteasome degradation system and mediates cellular processes, such as cell cycle, proliferation, and differentiation. UBE2T has been considered to be an oncogene in a variety of tumors. However, the oncogenic role of UBE2T in cervical cancer remains unclear. In this study, our results first showed that the expression of UBE2T was higher in both of cervical cancer tissues and cells than that in the normal tissues and cells. Knockdown of UBE2T reduced cervical cancer cell viability and suppressed the proliferation, invasion, and migration. However, overexpression of UBE2T contributed to cervical cancer cell growth and metastasis. Moreover, UBE2T overexpression cervical cancer cells demonstrated enhanced self-renewal capacity with upregulation of SOX2, Oct-4, and Nanog protein. Silencing of UBE2T downregulated protein expression of SOX2, Oct-4, and Nanog in cervical cancer cells reduced self-renewal capacity. Furthermore, ectopic UBE2T expression promoted protein expression of glucose-regulated protein 78 (GRP78) and focal adhesion kinase (FAK) phosphorylation in cervical cancer cells. The knockdown of UBE2T reduced protein expression of GRP78 and FAK phosphorylation. Collectively, UBE2T promoted cervical cancer stem cell traits and exerted an oncogenic role through activation of the GRP78/FAK pathway.

Inhibition of EGFR nuclear translocation attenuate radioresistance through decreased p-DNA-PK expression in cervical cancer cells.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17011-e17011
Author(s):  
Yunxiang Qi ◽  
Jinyi Lang ◽  
Lu Li ◽  
Mei Feng ◽  
Yecai Huang
Keyword(s):  
Cervical Cancer ◽  
Dna Damage ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Dna Damage Repair ◽  
Cervical Cancer Cell Line ◽  
Phosphorylation Level ◽  
Damage Repair ◽  
Cervical Cancer Cells

e17011 Background: The commonly used treatment for cervical cancer is radiotherapy. However, the resistance to irradiation and metastasis at the advanced stage is a common reason for the poor prognosis and high mortality. This study was designed to elucidate the role of epidermal growth factor receptor (EGFR) nuclear translocation in radioresistance, and its correlation with DNA damage repair pathway in the cervical cancer cells. Methods: The dynamic expression of EGFR, DNA-dependent protein kinase (DNA-PK), PDK-1, PKN1 and their phosphorylation level in irradiated cervical cancer cell line CaSki at 0 10 20 40 minutes was determined by western blotting. Besides, nuclear localization signal (NLS) peptide inhibitor and control peptides was synthesized and treated cells before irradiation to elucidate the correlation between EGFR nuclear translocation and DNA damage repair after irradiation. Results: Expression of EGFR, protein kinase N1 (PKN1), and DNA-PK in nucleus was increased after irradiation in CaSki cells. Irradiation also enhanced the phosphorylation level of EGFR at Thr654, PKN1 at T774 and DNA-PK at T2609. Inhibition of EGFR nuclear translocation by NLS peptide decreased the expression level of EGFR and DNA-PK in the nucleus, and attenuated their phosphorylation process. Conclusions: EGFR nuclear translocation riggered by irradiation promoted DNA damage repair in irradiated cervical cancer cells. This work facilitated us to understand the possible molecular mechanism of the resistance to irradiation in the treatment of cervical cancer, providing a potentially potent clinical method to cancer therapy.

scholarly journals The nuclear export of TR3 mediated gambogic acid-induced apoptosis in cervical cancer cells through mitochondrial dysfunction

RSC Advances ◽  
2019 ◽  
Vol 9 (21) ◽  
pp. 11855-11864
Author(s):  
Chunhong Zhang ◽  
Jia Liu ◽  
Fengxing Tao ◽  
Yiyi Lu ◽  
Qin He ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Nuclear Export ◽  
Gambogic Acid ◽  
Cervical Cancer Cells ◽  
Induced Apoptosis

The crosstalk of TR3 and p53 mediates GA-induced apoptosis of cervical cancer cells.

scholarly journals AURKA/NFκB Axis: A Key Determinant of Radioresistance in Cervical Squamous Carcinoma Cells

2021 ◽  
Author(s):  
Salini Das ◽  
Dilip Kumar Ray ◽  
Elizabeth Mahapatra ◽  
Souvick Biswas ◽  
Madhumita Roy ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cellular Proliferation ◽  
Nuclear Translocation ◽  
Squamous Carcinoma ◽  
Aurora Kinase ◽  
Therapy Resistance ◽  
Squamous Carcinoma Cells ◽  
Cervical Cancer Cells ◽  
Induced Apoptosis

Abstract Background: Cervical cancer being one of the leading gynaecological cancers, possess a major threat by its ever-increasing trend of global recurrence events. Radioresistance is one of the major challenges confronted during the treatment of cervical cancer. Radioresistance in cancer cells is manifested by increased rate of cellular proliferation, migration-invasion and cell cycle alterations. Aurora Kinase A (AURKA), a mitotic serine/threonine kinase was found to be overexpressed in cancers and is associated with development of acquired therapy resistance. The principal objective of this study revolved with exploring the mechanisms by which AURKA confers radioadaptive response in cervical cancer cells. Methods and Results: Parental cervical squamous carcinoma cell line SiHa was subjected to recurrent insult by fractionated dose of X-irradiation. Finally, a resistant subline (SiHa/RR) was isolated at 40Gy. SiHa/RR exhibited higher expression of AURKA/ pAURKA along with the signaling molecules that are favored by this kinase (HIF1α, pAkt, NFκB) vis-à-vis lower expressions of the molecules that are generally suppressed by AURKA (p53, Gadd45a). Surprisingly, inhibition of AURKA in SiHa/RR showed improved radiosensitivity by reducing the wound healing capacity, sphere forming ability and enhancing radiation induced apoptosis. Ectopic overexpression of AURKA gave rise to radioresistant phenotype in parental SiHa by stimulating nuclear translocation of NFκB. This pattern of increased nuclear localization of NFκB was also observed in resistant subline as a consequence of activation and overexpression of AURKA. Conclusion: These findings strengthened the involvement of AURKA in radioresistance via activating NFκB mediated signaling pathway to deliver radioresistant associated adaptive complexities.

scholarly journals Retraction: The nuclear export of TR3 mediated gambogic acid-induced apoptosis in cervical cancer cells through mitochondrial dysfunction

RSC Advances ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 4443-4443
Author(s):  
Laura Fisher
Keyword(s):  
Cervical Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Nuclear Export ◽  
Gambogic Acid ◽  
Cervical Cancer Cells ◽  
Induced Apoptosis

Retraction of ‘The nuclear export of TR3 mediated gambogic acid-induced apoptosis in cervical cancer cells through mitochondrial dysfunction’ by Chunhong Zhang et al., RSC Adv., 2019, 9, 11855–11864, DOI: 10.1039/C8RA10542A.

Sign in / Sign up

Export Citation Format

Share Document