Insulin-like growth factor I receptor regulates the radiation-induced G2/M checkpoint in HeLa cells

Manila, Nisha Gowri; Kaida, Atsushi; Nakahama, Ken-ichi; Miura, Masahiko

doi:10.1016/j.bbrc.2018.08.080

Cited by 5 publications

(8 citation statements)

References 30 publications

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“…Manila et al . demonstrated that IGF‐1 decreases radiation‐induced phosphorylation of Chk1 at S345 or S296 via the PI3K/AKT pathway . Notably, various studies have confirmed that KLF5 plays critical roles in the PI3K/Akt/mTOR pathway .…”

Section: Discussionmentioning

confidence: 99%

“…Manila et al demonstrated that IGF-1 decreases radiation-induced phosphorylation of Chk1 at S345 or S296 via the PI3K/AKT pathway. 27 Notably, various studies have confirmed that KLF5 plays critical roles in the PI3K/Akt/mTOR pathway. 11,13 Moreover, phosphorylation of Chk2 at T68 in response to DNA damage occurs in ATM-deficient cells, suggesting that kinases other than ATM may be involved.…”

Section: Discussionmentioning

confidence: 99%

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Knockdown of KLF5 promotes cisplatin‐induced cell apoptosis via regulating DNA damage checkpoint proteins in non‐small cell lung cancer

et al. 2019

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Background Previous research has revealed that Krüppel‐like factor 5 ( KLF5 ) may affect DNA damage repair pathways; however, the associated molecular mechanisms are unclear. Methods The expression of KLF5 was studied by immunohistochemical staining in paired tumour and normal tissues from 90 patients with ESCC. We studied the effects of KLF5 knockdown on cell proliferation and apoptosis with or without cisplatin treatment in A549 and H1299 cell lines. Moreover, we examined the effect of KLF5 on the DNA damage response. Results KLF5 was significantly overexpressed in non‐small cell lung cancer (NSCLC) tissues, and high KLF5 expression predicted poor prognosis for NSCLC patients. The inhibition of KLF5 markedly augmented cisplatin‐induced cell apoptosis. In addition, we observed that KLF5 knockdown could decrease DNA repair potential by inhibiting H2AX S139 phosphorylation in response to cisplatin. Moreover, silencing of KLF5 in NSCLC cell lines inhibited the phosphorylation of checkpoint kinases Chk1 S345 and Chk2 T68. KLF5 knockdown permits cells with broken or damaged DNA strands to enter mitosis by inhibiting the activation of H2AX, Chk1 and Chk2, resulting in mitotic catastrophe. Conclusion KLF5 plays a significant role in the DNA damage response by regulating DNA damage checkpoint proteins. Inhibition of KLF5 may be a potential therapeutic target for NSCLC patients with cisplatin resistance.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Knockdown of KLF5 promotes cisplatin‐induced cell apoptosis via regulating DNA damage checkpoint proteins in non‐small cell lung cancer

et al. 2019

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“…Irradiation. Cells were irradiated as described previously 33 , using a Clinac 6EX linear accelerator (Varian Medical Systems, Palo Alto, CA, USA) with a photon beam of nominal energy of 4 MV at a dose rate of 2.4 Gy/ min. Calibration was performed at the isocenter underneath an acrylic plate of 5-cm thickness for a field size of 20 cm × 20 cm.…”

Section: Methodsmentioning

confidence: 99%

Fluctuation in radioresponse of HeLa cells during the cell cycle evaluated based on micronucleus frequency

Shimono

Kaida

Homma

et al. 2020

Sci Rep

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In this study, we examined the fluctuation in radioresponse of HeLa cells during the cell cycle. For this purpose, we used HeLa cells expressing two types of fluorescent ubiquitination-based cell cycle indicators (Fucci), HeLa-Fucci (CA)2 and HeLa-Fucci (SA), and combined this approach with the micronucleus (MN) assay to assess radioresponse. The Fucci system distinguishes cell cycle phases based on the colour of fluorescence and cell morphology under live conditions. Time-lapse imaging allowed us to further identify sub-positions within the G1 and S phases at the time of irradiation by two independent means, and to quantitate the number of MNs by following each cell through M phase until the next G1 phase. Notably, we found that radioresponse was low in late G1 phase, but rapidly increased in early S phase. It then decreased until late S phase and increased in G2 phase. For the first time, we demonstrated the unique fluctuation of radioresponse by the MN assay during the cell cycle in HeLa cells. We discuss the difference between previous clonogenic experiments using M phase-synchronised cell populations and ours, as well as the clinical implications of the present findings.

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“…Activated ATM and ATR induce the phosphorylation and activation of Chk1/2 kinases, resulting in phosphorylation of CDC25C at Ser216, thereby inhibiting CDC2 kinase activity, and blocking activation of the CDK1/cyclin B complex. Finally, cells arrest at the G2/M boundary ( Figure 1; Manila et al, 2018;Yan et al, 2015).…”

Section: Cell-cycle Progression Following Rtmentioning

confidence: 99%

“…In HeLa cells, the insulin-like growth factor I receptor (IGF-IR) is putatively implicated in the radiation-induced G2/M checkpoint via the PI3K/ AKT pathway, without affecting DSB repair activities, in part by controlling Chk1 localisation between the nucleus and cytoplasm. An IGF-IR inhibitor (NVP-AEW541) caused delayed release from radiation-induced G2 arrest (Manila et al, 2018). The mTORC1specific inhibitor, RAD001, increased the sensitivity of SCC4 (human tongue squamous cell carcinoma) cells to X-rays, by suppressing mTOR signalling and inducing G2/M cell-cycle arrest through the Chk1/CDC25C/CDC2-cyclinB1 pathway (Sunada et al, 2018).…”

Section: Pi3k/akt/mtor Inhibitorsmentioning

confidence: 99%

Harnessing the targeting potential of differential radiobiological effects of photon versus particle radiation for cancer treatment

Zhang

Gan

et al. 2020

Journal Cellular Physiology

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Radiotherapy is one of the major modalities for malignancy treatment. High linear energy transfer (LET) charged-particle beams, like proton and carbon ions, exhibit favourable depth-dose distributions and radiobiological enhancement over conventional low-LET photon irradiation, thereby marking a new era in high precision medicine. Tumour cells have developed multicomponent signal transduction networks known as DNA damage responses (DDRs), which initiate cell-cycle checkpoints and induce double-strand break (DSB) repairs in the nucleus by nonhomologous end joining or homologous recombination pathways, to manage ionising radiation (IR)-induced DNA lesions. DNA damage induction and DSB repair pathways are reportedly dependent on the quality of radiation delivered. In this review, we summarise various types of DNA lesion and DSB repair mechanisms, upon irradiation with low and high-LET radiation, respectively. We also analyse factors influencing DNA repair efficiency. Inhibition of DNA damage repair pathways and dysfunctional cell-cycle checkpoint sensitises tumour cells to IR.

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Insulin-like growth factor I receptor regulates the radiation-induced G2/M checkpoint in HeLa cells

Cited by 5 publications

References 30 publications

Knockdown of KLF5 promotes cisplatin‐induced cell apoptosis via regulating DNA damage checkpoint proteins in non‐small cell lung cancer

Knockdown of KLF5 promotes cisplatin‐induced cell apoptosis via regulating DNA damage checkpoint proteins in non‐small cell lung cancer

Fluctuation in radioresponse of HeLa cells during the cell cycle evaluated based on micronucleus frequency

Harnessing the targeting potential of differential radiobiological effects of photon versus particle radiation for cancer treatment

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