The Role of YY1 in Oncogenesis and Its Potential as a Drug Target in Cancer Therapies

Shi, Jinming; Hao, Aixin; Zhang, Qiang; Sui, Guangchao

doi:10.2174/1568009615666150131124200

Cited by 60 publications

(56 citation statements)

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“…In normal intestine, YY1 has been shown to be indispensable for Lgr5+ intestinal stem cell renewal and de‐activating mutations in YY1 result in stem cell loss from apoptosis and accelerated differentiation . Evidence provided by us and others support a critical role of the multifunctional transcription factor YY1 in oncogenesis . YY1 overexpression detected in CRC and several other solid and hematological malignancies is linked to tumor growth, proliferation, migration, and metastasis .…”

Section: Discussionmentioning

confidence: 84%

CRHR2/Ucn2 signaling is a novel regulator of miR‐7/YY1/Fas circuitry contributing to reversal of colorectal cancer cell resistance to Fas‐mediated apoptosis

Pothoulakis

Torre-Rojas

Durán-Padilla

et al. 2017

Intl Journal of Cancer

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Colorectal cancer (CRC) responds poorly to immuno-mediated cytotoxicity. Underexpression of corticotropin-releasing-hormone-receptor-2 (CRHR2) in CRC, promotes tumor survival, growth and Epithelial to Mesenchymal Transition (EMT), in vitro and in vivo. We explored the role of CRHR2 downregulation in CRC cell resistance to Fas/FasL-mediated apoptosis and the underlying molecular mechanism. CRC cell sensitivity to CH11-induced apoptosis was compared between Urocortin-2 (Ucn2)-stimulated parental and CRHR2-overexpressing CRC cell lines and targets of CRHR2/Ucn2 signaling were identified through in vitro and ex vivo analyses. Induced CRHR2/Ucn2 signaling in SW620 and DLD1 cells increased specifically their sensitivity to CH11-mediated apoptosis, via Fas mRNA and protein upregulation. CRC compared to control tissues had reduced Fas expression that was associated with lost CRHR2 mRNA, poor tumor differentiation and high risk for distant metastasis. YY1 silencing increased Fas promoter activity in SW620 and re-sensitized them to CH11-apoptosis, thus suggesting YY1 as a putative transcriptional repressor of Fas in CRC. An inverse correlation between Fas and YY1 expression was confirmed in CRC tissue arrays, while elevated YY1 mRNA was clinically relevant with advanced CRC grade and higher risk for distant metastasis. CRHR2/Ucn2 signaling downregulated specifically YY1 expression through miR-7 elevation, while miR-7 modulation in miR-7 SW620-CRHR2+ and miR-7 HCT116 cells, had opposite effects on YY1 and Fas expressions and cell sensitivity to CH11-killing. CRHR2/Ucn2 signaling is a negative regulator of CRC cell resistance to Fas/FasL-apoptosis via targeting the miR-7/YY1/Fas circuitry. CRHR2 restoration might prove effective in managing CRC response to immune-mediated apoptotic stimuli.

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Section: Discussionmentioning

confidence: 84%

CRHR2/Ucn2 signaling is a novel regulator of miR‐7/YY1/Fas circuitry contributing to reversal of colorectal cancer cell resistance to Fas‐mediated apoptosis

Pothoulakis

Torre-Rojas

Durán-Padilla

et al. 2017

Intl Journal of Cancer

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“…37 It has been estimated that YY1 may regulate about 10% of mammalian gene expressions. 40,41 In human breast cancer tissues, YY1 expression is increased, and high expression of YY1 protein level is associated with poor prognosis of breast cancer in human. 40,41 In human breast cancer tissues, YY1 expression is increased, and high expression of YY1 protein level is associated with poor prognosis of breast cancer in human.…”

Section: Discussionmentioning

confidence: 99%

FAM3C‐YY1 axis is essential for TGFβ‐promoted proliferation and migration of human breast cancer MDA‐MB‐231 cells via the activation of HSF1

Yang

Feng

Meng

et al. 2019

J Cellular Molecular Medi

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Family with sequence similarity three member C (FAM3C) (interleukin‐like EMT inducer [ILEI]), heat shock factor 1 (HSF1) and Ying‐Yang 1 (YY1) have been independently reported to be involved in the pathogenesis of various cancers. However, whether they are coordinated to trigger the development of cancer remains unknown. This study determined the role and mechanism of YY1 and HSF1 in FAM3C‐induced proliferation and migration of breast cancer cells. In human MDA‐MB‐231 breast cancer cell line, transforming growth factor‐β (TGFβ) up‐regulated FAM3C, HSF1 and YY1 expressions. FAM3C overexpression promoted the proliferation and migration of MDA‐MB‐231 cells with YY1 and HSF1 up‐regulation, whereas FAM3C silencing exerted the opposite effects. FAM3C inhibition repressed TGFβ‐induced HSF1 activation, and proliferation and migration of breast cancer cells. YY1 was shown to directly activate HSF1 transcription to promote the proliferation and migration of breast cancer cells. YY1 silencing blunted FAM3C‐ and TGFβ‐triggered activation of HSF1‐Akt‐Cyclin D1 pathway, and proliferation and migration of breast cancer cells. Inhibition of HSF1 blocked TGFβ‐, FAM3C‐ and YY1‐induced proliferation and migration of breast cancer cells. YY1 and HSF1 had little effect on FAM3C expression. Similarly, inhibition of HSF1 also blunted FAM3C‐ and TGFβ‐promoted proliferation and migration of human breast cancer BT‐549 cells. In human breast cancer tissues, FAM3C, YY1 and HSF1 protein expressions were increased. In conclusion, FAM3C activated YY1‐HSF1 signalling axis to promote the proliferation and migration of breast cancer cells. Furthermore, novel FAM3C‐YY1‐HSF1 pathway plays an important role in TGFβ‐triggered proliferation and migration of human breast cancer MDA‐MB‐231 cells.

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“…Furthermore, the ability of CP2c to be engaged in physical interaction with various partner proteins further increases functional complexity of this protein [6–11]. Similarly, YY1 has multiple critical roles in various biological processes, ranging from cell proliferation to cell differentiation, and from cancer progression to embryogenesis [25–28]. It is likely that the highly disordered nature of these two TFs hold an answer to the question on their polyfunctionality.…”

Section: Discussionmentioning

confidence: 99%

“…Like CP2c, YY1 is a ubiquitously expressed TF involved in diverse biological processes, such as embryogenesis, differentiation, proliferation, and cancer progression [25–28]. YY1 is well known for its dual roles in regulating gene expression, either as an activator or repressor, depending on the chromatin remodeling complexes it is recruited to [29].…”

Section: Introductionmentioning

confidence: 99%

Diagnostic and prognostic relevance of CP2c and YY1 expression in hepatocellular carcinoma

et al. 2017

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Recent studies have demonstrated an oncogenic role of the transcription factor (TF) CP2c in hepatocellular carcinoma (HCC) based on a strong correlation between CP2c expression, tumor grade, and aggressiveness. We recently found that CP2c directly interacts with another TF, YY1, which is also overexpressed in multiple cancers, including HCC. To evaluate if these proteins are co-regulated in carcinogenesis, we analyzed the expression of CP2c and YY1 in HCC (n = 136) tissues and examined the correlation between their expression and clinicopathological characteristics of HCC. Receiver operating characteristic analysis exhibited the validity of CP2c and nuclear YY1 expression as a diagnostic factor in HCC tissues. High expression of CP2c was significantly correlated with patient age, and higher histological grade, American Joint Committee on Cancer (AJCC) stage, and small and large vessel invasion in HCC tissues, whereas high expression of nuclear YY1 was significantly associated with higher AJCC stage and small vessel invasion. In univariate and multivariate analyses, high expression of CP2c was significantly correlated with disease free survival (DFS), indicating that CP2c expression is an independent prognostic factor for DFS in HCC patients. Patients with high expression of both CP2c and nuclear YY1 usually had a shorter median survival time and worse DFS prognosis than other patients, suggesting that combined detection of CP2c and nuclear YY1 is a useful prognostic marker in HCC patients.

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The Role of YY1 in Oncogenesis and Its Potential as a Drug Target in Cancer Therapies

Cited by 60 publications

References 0 publications

CRHR2/Ucn2 signaling is a novel regulator of miR‐7/YY1/Fas circuitry contributing to reversal of colorectal cancer cell resistance to Fas‐mediated apoptosis

CRHR2/Ucn2 signaling is a novel regulator of miR‐7/YY1/Fas circuitry contributing to reversal of colorectal cancer cell resistance to Fas‐mediated apoptosis

FAM3C‐YY1 axis is essential for TGFβ‐promoted proliferation and migration of human breast cancer MDA‐MB‐231 cells via the activation of HSF1

Diagnostic and prognostic relevance of CP2c and YY1 expression in hepatocellular carcinoma

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