The role of CIP2A as a therapeutic target of rapamycin in radioresistant head and neck cancer with TP53 mutation

Kim, Song Hee; Lee, Won Hyeok; Seong, Daseul; An, Jae Hee; Je, Hyoung Uk; Nam, Hae Yun; Kim, Sang Yoon; Kim, Seong Who; Han, Myung Woul

doi:10.1002/hed.25868

Cited by 6 publications

(4 citation statements)

References 38 publications

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“…p53 inhibits the expression of CIP2A. Kim et al ( 73 ) indicated that CIP2A modulates the radioresistance of cancer cells by attenuating cell senescence in HNSCC through disruption caused by p53 mt . They irradiated HNSCC cell lines carrying different p53 mutants to determine their effects on cell survival and CIP2A expression levels, and they observed that CIP2A is highly expressed in radioresistant HNSCC cells carrying disruptive p53 mt .…”

Section: Mutant P53 and Its Target Genesmentioning

confidence: 99%

Relationship between p53 status and the bioeffect of ionizing radiation (Review)

Kong

Wang

et al. 2021

Oncol Lett

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Radiotherapy is widely used in the clinical treatment of cancer patients and it may be used alone or in combination with surgery or chemotherapy to inhibit tumor development. However, radiotherapy may at times not kill all cancer cells completely, as certain cells may develop radioresistance that counteracts the effects of radiation. The emergence of radioresistance is associated with the genetic background and epigenetic regulation of cells. p53 is an important tumor suppressor gene that is expressed at low levels in cells. However, when cells are subjected to stress-induced stimulation, the expression level of p53 increases, thereby preventing genomic disruption. This mechanism has important roles in maintaining cell stability and inhibiting carcinogenesis. However, mutation and deletion destroy the anticancer function of p53 and may induce carcinogenesis. In tumor radiotherapy, the status of p53 expression in cancer cells has a close relationship with radiotherapeutic efficacy. Therefore, understanding how p53 expression affects the cellular response to radiation is of great significance for solving the problem of radioresistance and improving radiotherapeutic outcomes. For the present review, the literature was searched for studies published between 1979 and 2021 using the PubMed database ( ) with the following key words: Wild-type p53, mutant-type p53, long non-coding RNA, microRNA, gene mutation, radioresistance and radiosensitivity. From the relevant studies retrieved, the association between different p53 mutants and cellular radiosensitivity, as well as the molecular mechanisms of p53 affecting the radiosensitivity of cells, were summarized. The aim of the present study was to provide useful information for understanding and resolving radioresistance, to help clinical researchers develop more accurate treatment strategies and to improve radiotherapeutic outcomes for cancer patients with p53 mutations.

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Section: Mutant P53 and Its Target Genesmentioning

confidence: 99%

Relationship between p53 status and the bioeffect of ionizing radiation (Review)

Kong

Wang

et al. 2021

Oncol Lett

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“…Furthermore, Cip2A is regulated protein expression by the mitogen‐activated protein kinase kinase (MEK)/extracellular signal‐regulated kinase (ERK) pathways 10,11 . Although the oncogenic role of CIP2A in various cancers has been reported, the mechanisms underlying its oncogenic effects are still unclear 5,12–15 …”

Section: Introductionmentioning

confidence: 99%

Cip2A modulates osteogenic differentiation via the ERK‐Runx2 pathway in MG63 cells

Son

Jang

2021

BioFactors

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Cancerous inhibitor of protein phosphatase 2A (Cip2A) is an oncoprotein that promotes the development of several types of cancer. However, its molecular function in osteoblast differentiation remains unclear. In this study, we found that Cip2A was upregulated under osteogenic conditions in MG63 cells. Besides, overexpression of Cip2A significantly increased the expression of Runt‐related transcription factor 2 (Runx2) and alkaline phosphatase (ALP). Inversely, the knockdown of Cip2A in MG63 cells suppressed osteoblast differentiation. Cip2A expression during osteogenic differentiation was mediated by extracellular signal‐regulated kinase (ERK) activation. Taken together, our results suggest that Cip2A plays important role in regulating osteoblast differentiation by inducing ERK phosphorylation in MG63 cells.

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“…Bortezomib, a proteasome inhibitor active in the treatment of multiple myeloma and mantle cell lymphoma, has been evaluated in cell lines in HNSCC HPV +, demonstrating its ability to restore p53 function and hypothetical restore radiosensitivity via p21/p53 transactivation. However, in combination with radiotherapy or chemotherapy with Cisplatin, Bortezomide has no radiosensitivity and chemo-sensitivity modulator effect on HNSCC HPV+ and HPV- cell lines [ 2 , 104 , 105 , 106 , 107 , 108 , 109 , 110 ].…”

Section: P53 New Horizons For Head Neck Cancer Treatmentmentioning

confidence: 99%

“…BYL719 (alpelisib), a PI3Kα-selective inhibitor, is proposed as a therapy for restoring radiosensitivity by breaking the C-MYC p53 bond. A chemical chaperone (glycerol) has the potential to restore p53 function on HNSCC cell lines, being considered an agent with a possible role in p53-mediated radiosensitization [ 107 , 108 , 109 ].…”

Section: P53 New Horizons For Head Neck Cancer Treatmentmentioning

confidence: 99%

p53 Modulates Radiosensitivity in Head and Neck Cancers—From Classic to Future Horizons

Mireștean

Iancu

2022

Diagnostics

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p53, initially considered a tumor suppressor, has been the subject of research related to cancer treatment resistance in the last 30 years. The unfavorable response to multimodal therapy and the higher recurrence rate, despite an aggressive approach, make HNSCC a research topic of interest for improving therapeutic outcomes, even if it is only the sixth most common malignancy worldwide. New advances in molecular biology and genetics include the involvement of miRNA in the control of the p53 pathway, the understanding of mechanisms such as gain/loss of function, and the development of different methods to restore p53 function, especially for HPV-negative cases. The different ratio between mutant p53 status in the primary tumor and distant metastasis originating HNSCC may serve to select the best therapeutic target for activating an abscopal effect by radiotherapy as a “booster” of the immune system. P53 may also be a key player in choosing radiotherapy fractionation regimens. Targeting any pathway involving p53, including tumor metabolism, in particular the Warburg effect, could modulate the radiosensitivity and chemo-sensitivity of head and neck cancers.

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The role of CIP2A as a therapeutic target of rapamycin in radioresistant head and neck cancer with TP53 mutation

Cited by 6 publications

References 38 publications

Relationship between p53 status and the bioeffect of ionizing radiation (Review)

Relationship between p53 status and the bioeffect of ionizing radiation (Review)

Cip2A modulates osteogenic differentiation via the ERK‐Runx2 pathway in MG63 cells

p53 Modulates Radiosensitivity in Head and Neck Cancers—From Classic to Future Horizons

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