RhoBTB2 (DBC2) functions as tumor suppressor via inhibiting proliferation, preventing colony formation and inducing apoptosis in breast cancer cells

Mao, Hongzhi; Zhang, Lining; Yang, Yongmei; Sun, Jia; Deng, Biping; Jiao, Feng; Shao, Qianqian; Feng, Alei; Song, Bingfeng; Qu, Xun

doi:10.1016/j.gene.2011.07.018

Cited by 22 publications

(12 citation statements)

References 36 publications

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“…Finally, Lats2 is a negative regulator of cell growth and a tissue-specific inhibitor of cell size (28–30). Similar to Foxm1 , p53 remained bound to a Lats2 p53RE at 24h post-PH (Fig.…”

Section: Resultsmentioning

confidence: 99%

p53 regulates a mitotic transcription program and determines ploidy in normal mouse liver

et al. 2013

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Functions of p53 during mitosis reportedly include prevention of polyploidy and transmission of aberrant chromosomes. However, whether p53 plays these roles during genomic surveillance in vivo and, if so, by direct or indirect means remain unknown. The ability of normal, mature hepatocytes to respond to stimuli, reenter cell cycle and regenerate liver mass offers an ideal setting to assess mitosis in vivo. In quiescent liver, normally high ploidy levels in adult mice increased with loss of p53. Following partial hepatectomy, p53−/− hepatocytes exhibited early entry into cell cycle and prolonged proliferation with an increased number of polyploid mitoses. Ploidy levels increased during regeneration of both WT and p53−/− hepatocytes, but only WT hepatocytes were able to dynamically resolve ploidy levels and return to normal by the end of regeneration. We identified multiple cell cycle and mitotic regulators, including Foxm1, Aurka, Lats2, Plk2 and Plk4, as directly regulated by chromatin interactions of p53 in vivo. Over a time course of regeneration, direct and indirect regulation of expression by p53 is mediated in a gene-specific manner. Conclusion Our results show that p53 plays a role in mitotic fidelity and ploidy resolution in hepatocytes of normal and regenerative liver.

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“…Finally, Lats2 is a negative regulator of cell growth and a tissue-specific inhibitor of cell size (28–30). Similar to Foxm1 , p53 remained bound to a Lats2 p53RE at 24h post-PH (Fig.…”

Section: Resultsmentioning

confidence: 99%

p53 regulates a mitotic transcription program and determines ploidy in normal mouse liver

et al. 2013

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“…Downregulation of RhoBTB2 was further observed in lung, bladder, bone and gastric cancer (Cho et al 2009;Shi et al 2008;Dong et al 2012;Jin et al 2013). Obtained in breast cancer cells, evidence suggests that RhoBTB2 exerts a tumor-suppressive function by inhibiting cancer cell proliferation, migration and invasiveness (Ling et al 2014;Mao et al 2011). Similar anti-tumorigenic properties were also found for the other RhoBTB isoforms.…”

Section: Rhobtb Lkb1 (Stk11) Hippo Pathway Ubiquitinationmentioning

confidence: 63%

RhoBTB Proteins Regulate the Hippo Pathway by Antagonizing Ubiquitination of LKB1

Nguyen

Ralbovska

Kugler

2020

G3 Genes|Genomes|Genetics

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The Hippo pathway regulates growth and apoptosis. We identify RhoBTB proteins as novel regulators of Hippo signaling. RhoBTB depletion in the Drosophila wing disc epithelium cooperated with Yki to drive hyperplasia into neoplasia. Depletion of RhoBTB2 caused elevated YAP activity in human cells. RhoBTB2 deficiency resulted in increased colony formation in assays for anchorage-independent growth. We provide evidence that RhoBTBs acts on Hippo signaling through regulation of the kinase LKB1. LKB1 protein levels were reduced upon RhoBTB2 depletion, which correlated with increased LKB1 ubiquitination. Restoring LKB1 levels rescued loss of RhoBTB in Drosophila. Our results suggest that RhoBTB-dependent LKB1 regulation may contribute to its tumor-suppressive function.

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“…Recent researches indicate that DBC2 participates in diverse cellular activities, significantly influences cellcycle, apoptosis, cytoskeleton and membrane-trafficking pathways (Siripurapu et al, 2005;Chang et al, 2006). DBC2 really plays as an important tumor suppressor gene by inhibiting proliferation, preventing colony formation and promoting the apoptosis of tumor cells (Mao et al, 2011). Successive studies showed that the downregulation of DBC2 was found in 58% (11/19) of breast, 50% (7/14) of lung, and 75% (9/12) of bladder tumor cell lines (Knowles et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Loss of DBC2 Expression is an Early and Progressive Event in the Development of Lung Adenocarcinoma

Wang

Li²,

Shen³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Purpose: DBC2 (Deleted in Breast Cancer 2) has been indicated to be a tumor suppressor gene in many cancers including lung adenocarcinoma recently. In this study, we aimed to explore the expression status of DBC2 in different subtypes of lung adenocarcinoma (from pre-invasive to invasive lesions), and to determine if downregulation becomes more marked with pathological progression. Methods: We collected 172 tissue samples from different subtypes of lung adenocarcinoma and investigated the frequency of DBC2 loss by immunohistochemistry. Results: Our results indicated that DBC2 downregulation is a relatively frequent event in lung adenocarcinoma. Moreover, as the adenocarcinoma subtype turns to be more invasive, more downregulation occurred. Conclusion: We conclude that loss of DBC2 expression is an early and progressive event in the pathogenesis of lung adenocarcinoma. Positive DBC2 immunohistochemistry may become an indicator for early stage disease and better prognosis of lung adenocarcinomas.

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RhoBTB2 (DBC2) functions as tumor suppressor via inhibiting proliferation, preventing colony formation and inducing apoptosis in breast cancer cells

Cited by 22 publications

References 36 publications

p53 regulates a mitotic transcription program and determines ploidy in normal mouse liver

p53 regulates a mitotic transcription program and determines ploidy in normal mouse liver

RhoBTB Proteins Regulate the Hippo Pathway by Antagonizing Ubiquitination of LKB1

Loss of DBC2 Expression is an Early and Progressive Event in the Development of Lung Adenocarcinoma

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