Transcriptional repression of cancer stem cell marker CD133 by tumor suppressor p53

Park, E K; Lee, J C; Park, J W; Bang, So Young; Yi, Sang Ah; Kim, B K; Park, J H; Kwon, So Hee; You, Jueng Soo; Nam, Suk Woo; Cho, Eun Jung; Han, Jiwon

doi:10.1038/cddis.2015.313

Cited by 88 publications

(72 citation statements)

References 58 publications

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“…The present study demonstrated that wild-type p53 transactivated the promoter of the CD133 gene, indicating that the CD133 gene may be a novel target of p53 in colorectal cancer. Although it was previously reported that p53 transcriptionally suppressed CD133 expression (35), p53 may function with different transcription factors in the context of colorectal cancer to maintain the stem cell properties of HCT116 cells, which may be independent of the tumor suppressor role of p53 in other types of cancer. The specificity and robustness of CD133 as a colorectal CSC marker may also need further investigation (36,37).…”

Section: Discussionmentioning

confidence: 99%

p53 positively regulates the expression of cancer stem cell marker CD133 in HCT116 colon cancer cells

et al. 2018

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Abstract. Colon cancer stem cells (CSCs), which are highly capable of self-renewal and proliferation, are involved in colon tumorigenesis and response to therapy. CD133 is considered the most robust surface marker for colorectal cancer stem cells. Although the TP53 gene is frequently mutated in colon cancer, it remains not fully understood whether and how tumor protein p53 (p53) is associated with CD133 expression in colon cancer cells. In the present study, the expression of the CSC biomarker CD133 was investigated in terms of p53 status in colorectal carcinoma HCT116 cells. p53 wild-type HCT116 (HCT116 p53 IntroductionColorectal carcinoma (CRC), which is prone to metastasis and recurrence, is a cancer with a high lethality rate worldwide. More than 50% of patients will develop metastasis and recurrence (1,2). Multiple factors account for metastasis and recurrence, including tumor stage, cancer subtypes and cancer stem cells (CSCs). CSCs are a small population of tumor-initiating cells that have the ability to self-renew and differentiate in tumors in vivo. CSCs are involved in various processes during tumor formation, progression, and angiogenesis and are considered an important target for novel cancer treatment strategies (3). Several specific surface markers are expressed on CSCs, including CD133, CD44 and aldehyde dehydrogenase 1 (ALDH1) (4). CD133 (also known as prominin-1) is a 5-transmembrane glycoprotein of 865 amino acids with a total molecular weight of 120 kDa. CD133 is a CSC marker in colon carcinoma. CD133-positive cells correlate strongly with poor prognosis and synchronous liver metastasis (5). Cancer cell populations with high expression of CD133 are much more aggressive in terms of metastases compared with those with low expression of CD133, suggesting that CD133 may be a marker of increased tumorigenesis ability. CD133-positive cells from clinical biopsy-derived cultures have been demonstrated to possess multilineage differentiation potential and are capable of tumor initiation in vivo. CD133-positive CRC cells are more resistant to chemoradiotherapy, and CD133 expression is associated with poor prognosis (6,7). However, the regulation of CD133 expression has not been fully elucidated.The present study demonstrated that CD133 expression was associated with the tumor protein p53 (p53) expression in an HCT116 p53 +/+ cell line. Of note, CD133-negative cells were detected in the colon cancer cell line HCT116 in a previous report by Kai et al (8

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Section: Discussionmentioning

confidence: 99%

p53 positively regulates the expression of cancer stem cell marker CD133 in HCT116 colon cancer cells

et al. 2018

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“…p53 recruits histone deacetylase 1 (HDAC1) to the CD133 promoter and reduces histone H3 acetylation. Reduction in CD133 expression inhibits tumor cell proliferation, colony formation and the expression of Nanog, Oct4, Sox2 and c-Myc stemness transcription factors [104]. …”

Section: Introductionmentioning

confidence: 99%

Emerging Non-Canonical Functions and Regulation by p53: p53 and Stemness

Olivos

Mayo

2016

IJMS

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Since its discovery nearly 40 years ago, p53 has ascended to the forefront of investigated genes and proteins across diverse research disciplines and is recognized most exclusively for its role in cancer as a tumor suppressor. Levine and Oren (2009) reviewed the evolution of p53 detailing the significant discoveries of each decade since its first report in 1979. In this review, we will highlight the emerging non-canonical functions and regulation of p53 in stem cells. We will focus on general themes shared among p53’s functions in non-malignant stem cells and cancer stem-like cells (CSCs) and the influence of p53 on the microenvironment and CSC niche. We will also examine p53 gain of function (GOF) roles in stemness. Mutant p53 (mutp53) GOFs that lead to survival, drug resistance and colonization are reviewed in the context of the acquisition of advantageous transformation processes, such as differentiation and dedifferentiation, epithelial-to-mesenchymal transition (EMT) and stem cell senescence and quiescence. Finally, we will conclude with therapeutic strategies that restore wild-type p53 (wtp53) function in cancer and CSCs, including RING finger E3 ligases and CSC maintenance. The mechanisms by which wtp53 and mutp53 influence stemness in non-malignant stem cells and CSCs or tumor-initiating cells (TICs) are poorly understood thus far. Further elucidation of p53’s effects on stemness could lead to novel therapeutic strategies in cancer research.

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“…HDACs operate by direct association with DNA-binding factors and by incorporation into large multifunctional repressor complexes such as Sin3, NuRD, and PRC2 [12]. In addition to functions in chromatin remodeling, HDACs deacetylate certain transcription factors, such as P53 [13], resulting in their decreased activity. HDACs form a large family, of which class I HDACs, including the closely related proteins HDAC1 and HDAC2, show the strongest histone deacetylase activity[14].…”

Section: Introductionmentioning

confidence: 99%

HDAC1 promoted migration and invasion binding with TCF12 by promoting EMT progress in gallbladder cancer

Shen

et al. 2016

Oncotarget

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The identification of prognostic markers for gallbladder cancer is needed for clinical practice. Histone deacetylases (HDACs) play an important role in tumor development and progression by modifying histone and non-histone proteins. However, the expression of HDAC1 in patients with gallbladder cancer is still unknown. Here, we reported that HDAC1 expression was elevated in cancerous tissue and correlated with lymph node metastasis and poorer overall survival in patients with GBC. Knockdown of HDAC1 using lentivirus delivery of HDAC1-specific shRNA abrogated the migration and invasion of GBC cells in vitro. TCF-12, as the HDAC1 binding protein, has also correlates with poor prognosis in GBC patients. And there is a positive correlation between HDAC1 and TCF-12 which leading the high invasion and migration ability of GBC cells. Taken together, our data suggested that HDAC1 and TCF-12 are a potential prognostic maker and may be a molecular target for inhibiting invasion and metastasis in GBC.

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Transcriptional repression of cancer stem cell marker CD133 by tumor suppressor p53

Cited by 88 publications

References 58 publications

p53 positively regulates the expression of cancer stem cell marker CD133 in HCT116 colon cancer cells

p53 positively regulates the expression of cancer stem cell marker CD133 in HCT116 colon cancer cells

Emerging Non-Canonical Functions and Regulation by p53: p53 and Stemness

HDAC1 promoted migration and invasion binding with TCF12 by promoting EMT progress in gallbladder cancer

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