Role of telomeric RAP1 in radiation sensitivity modulation and its interaction with CSC marker KLF4 in colorectal cancer

Anuja, Kumari; Kar, Madhabananda; Chowdhury, Amit Roy; Shankar, Gauri; Padhi, Swatishree; S, Roy; Akhter, Yusuf; Rath, Arabinda Kumar; Banerjee, Birendranath

doi:10.1080/09553002.2020.1721609

Cited by 14 publications

(14 citation statements)

References 57 publications

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“…Several groups have shown that RAP1 is highly variable across cancer types, and also in some cases within cancer types. Accordingly, the overexpression of RAP1 has been reported in breast cancer [25], gastric carcinoma [26], non-small cell lung cancer [27], mantle cell lymphoma [28], multiple melanoma [29], colorectal cancer [30], and renal cell carcinoma [31]. In familial papillary thyroid cancer [32], reduced expression of RAP1 has been described.…”

Section: Dysregulation Of Rap1 Expression In Cancermentioning

confidence: 99%

RAP1/TERF2IP—A Multifunctional Player in Cancer Development

Deręgowska

Wnuk

2021

Cancers

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Mammalian RAP1 (TERF2IP), the most conserved shelterin component, plays a pleiotropic role in the regulation of a variety of cellular processes, including cell metabolism, DNA damage response, and NF-κB signaling, beyond its canonical telomeric role. Moreover, it has been demonstrated to be involved in oncogenesis, progression, and chemoresistance in human cancers. Several mutations and different expression patterns of RAP1 in cancers have been reported. However, the functions and mechanisms of RAP1 in various cancers have not been extensively studied, suggesting the necessity of further investigations. In this review, we summarize the main roles of RAP1 in different mechanisms of cancer development and chemoresistance, with special emphasis on the contribution of RAP1 mutations, expression patterns, and regulation by non-coding RNA, and briefly discuss telomeric and non-telomeric functions.

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Section: Dysregulation Of Rap1 Expression In Cancermentioning

confidence: 99%

RAP1/TERF2IP—A Multifunctional Player in Cancer Development

Deręgowska

Wnuk

2021

Cancers

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“…In HCT116RR, derived radio-resistant cancer cells, KLF4 directly interacts with the human telomeric RAP1 protein [ 24 ]. The silencing of RAP1 reverses the radio-resistant phenotype in these cells and increases their sensitivity to radiotherapy.…”

Section: Colorectal Cancermentioning

confidence: 99%

“…The silencing of RAP1 reverses the radio-resistant phenotype in these cells and increases their sensitivity to radiotherapy. Increased RAP1 levels were associated with a poor survival rate, indicating that RAP1 could serve a marker for survival prediction in these types of cancer [ 24 ], although the precise relationship between RAP1 and KLF4 needs to be investigated further. B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI1) deficiency sensitizes cells to radiation treatment by modulating the expression of KLF4 and leads to enhanced radiosensitivity in microsatellite stable colorectal cancers [ 25 ].…”

Section: Colorectal Cancermentioning

confidence: 99%

Recent Discoveries on the Involvement of Krüppel-Like Factor 4 in the Most Common Cancer Types

Taracha-Wisniewska

Kotarba

Dworkin

et al. 2020

IJMS

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Krüppel-like factor 4 (KLF4) is a transcription factor highly conserved in evolution. It is particularly well known for its role in inducing pluripotent stem cells. In addition, KLF4 plays many roles in cancer. The results of most studies suggest that KLF4 is a tumor suppressor. However, the functioning of KLF4 is regulated at many levels. These include regulation of transcription, alternative splicing, miRNA, post-translational modifications, subcellular localization, protein stability and interactions with other molecules. Simple experiments aimed at assaying transcript levels or protein levels fail to address this complexity and thus may deliver misleading results. Tumor subtypes are also important; for example, in prostate cancer KLF4 is highly expressed in indolent tumors where it impedes tumor progression, while it is absent from aggressive prostate tumors. KLF4 is important in regulating response to many known drugs, and it also plays a role in tumor microenvironment. More and more information is available about upstream regulators, downstream targets and signaling pathways associated with the involvement of KLF4 in cancer. Furthermore, KLF4 performs critical function in the overall regulation of tissue homeostasis, cellular integrity, and progression towards malignancy. Here we summarize and analyze the latest findings concerning this fascinating transcription factor.

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“…At present, the mechanisms by which cancer cells acquire RR remain unclear. In the present study, obstacles in the treatment of BCa were considered to be attributed to the radiation tolerance of cancer stem cells (CSCs) present in the tumor (10,11). CSCs may be seen as a reservoir of cancer cells due to their self-renewal and plasticity properties, and the ability to reconstruct heterogeneous tumor cell populations (12).…”

Section: Introductionmentioning

confidence: 98%

STAT3 enhances radiation-induced tumor migration, invasion and stem-like properties of bladder cancer

Wang

Mao

et al. 2020

Mol Med Rep

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Bladder cancer (BCa) is the most common cancer of the human urinary system, and is associated with poor patient prognosis and a high recurrence rate. Cancer stem cells (CSCs) are the primary cause of tumor recurrence and metastasis, possessing self-renewal properties and resistance to radiation therapy. Our previous studies indicated that phosphorylated signal transduction and transcription activator 3 (STAT3) may be a potential biomarker to predict radiation tolerance and tumor recurrence in patients with BCa, following conventional radiotherapy. The aim of the present study was to investigate the underlying mechanism of STAT3 in the radio-resistance of BCa cells. It was found that fractionated irradiation promoted the activation of two STAT3-associated CSCs signaling pathways in BCa cells, namely suppressor of variegation 3-9 homolog 1/GATA binding protein 3/STAT3 and Janus kinase 2/STAT3. Surviving cells exhibited elevated migratory and invasive abilities, enhanced CSC-like characteristics and radio-resistance. Furthermore, knockdown of STAT3 expression or inhibition of STAT3 activation markedly decreased the self-renewal ability and tumorigenicity of radiation-resistant BCa cells. Kaplan-Meier analysis revealed that decreased STAT3 mRNA levels were associated with increased overall survival times in patients with BCa. Taken together, these data indicated that STAT3 may be an effective therapeutic target for inhibiting the progression, metastasis and recurrence of BCa in patients receiving radiotherapy.

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Role of telomeric RAP1 in radiation sensitivity modulation and its interaction with CSC marker KLF4 in colorectal cancer

Cited by 14 publications

References 57 publications

RAP1/TERF2IP—A Multifunctional Player in Cancer Development

RAP1/TERF2IP—A Multifunctional Player in Cancer Development

Recent Discoveries on the Involvement of Krüppel-Like Factor 4 in the Most Common Cancer Types

STAT3 enhances radiation-induced tumor migration, invasion and stem-like properties of bladder cancer

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