The family of apoptosis-stimulating proteins of p53 is dysregulated in colorectal cancer patients

Yin, Libin; Lin, Yuyang; Wang, Xu; Su, Yanzhuo; Hu, Han Hwa; Li, Chao; Wang, Lei; Jiang, Yanfang

doi:10.3892/ol.2018.8151

Cited by 12 publications

(17 citation statements)

References 42 publications

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“…Tumor apoptosis is a hallmark in the pathogenesis and treatment for human cancer patients ( 33 – 35 ). Li et al ( 36 ) indicated that growth arrest and apoptosis of the human hepatocellular carcinoma cell line BEL-7402 could be induced by melittin by up-regulation of Fas expression.…”

Section: Discussionmentioning

confidence: 99%

Melittin suppresses growth and induces apoptosis of non-small-cell lung cancer cells via down-regulation of TGF-β-mediated ERK signal pathway

Wang

Han

2021

Braz J Med Biol Res

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The purpose of this study was to investigate the anti-cancer effect of melittin on growth, migration, invasion, and apoptosis of non-small-cell lung cancer (NSCLC) cells. This study also explored the potential anti-cancer mechanism of melittin in NSCLC cells. The results demonstrated that melittin suppressed growth, migration, and invasion, and induced apoptosis of NSCLC cells in vitro. Melittin increased pro-apoptotic caspase-3 and Apaf-1 gene expression. Melittin inhibited tumor growth factor (TGF)-b expression and phosphorylated ERK/total ERK (pERK/tERK) in NSCLC cells. However, TGF-b overexpression (pTGF-b) abolished melittin-decreased TGF-b expression and pERK/tERK in NSCLC cells. Treatment with melittin suppressed tumor growth and prolonged mouse survival during the 120-day observation in vivo. Treatment with melittin increased TUNEL-positive cells and decreased expression levels of TGF-b and ERK in tumor tissue compared to the control group. In conclusion, the findings of this study indicated that melittin inhibited growth, migration, and invasion, and induced apoptosis of NSCLC cells through down-regulation of TGF-b-mediated ERK signaling pathway, suggesting melittin may be a promising anti-cancer agent for NSCLC therapy.

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Section: Discussionmentioning

confidence: 99%

Melittin suppresses growth and induces apoptosis of non-small-cell lung cancer cells via down-regulation of TGF-β-mediated ERK signal pathway

Wang

Han

2021

Braz J Med Biol Res

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“…Indeed, there is growing evidence that overexpression, rather than mutation, of iASPP conveys its oncogenic properties. In addition to our previous characterization in p53 wild-type breast cancer (32), elevated iASPP levels have recently been reported in multiple human cancers, including bladder cancer (63), non-small-cell lung cancer (64), ovarian clear cell carcinoma (65), colorectal cancer (66), and particularly in acute leukemia where p53 mutations are relatively rare (67, 68).…”

Section: Discussionmentioning

confidence: 67%

iASPP mediates p53 selectivity through a modular mechanism fine-tuning DNA recognition

Chen

Zhong

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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The most frequently mutated protein in human cancer is p53, a transcription factor (TF) that regulates myriad genes instrumental in diverse cellular outcomes including growth arrest and cell death. Cell context-dependent p53 modulation is critical for this life-or-death balance, yet remains incompletely understood. Here we identify sequence signatures enriched in genomic p53-binding sites modulated by the transcription cofactor iASPP. Moreover, our p53–iASPP crystal structure reveals that iASPP displaces the p53 L1 loop—which mediates sequence-specific interactions with the signature-corresponding base—without perturbing other DNA-recognizing modules of the p53 DNA-binding domain. A TF commonly uses multiple structural modules to recognize its cognate DNA, and thus this mechanism of a cofactor fine-tuning TF–DNA interactions through targeting a particular module is likely widespread. Previously, all tumor suppressors and oncoproteins that associate with the p53 DNA-binding domain—except the oncogenic E6 from human papillomaviruses (HPVs)—structurally cluster at the DNA-binding site of p53, complicating drug design. By contrast, iASPP inhibits p53 through a distinct surface overlapping the E6 footprint, opening prospects for p53-targeting precision medicine to improve cancer therapy.

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“…The role of ASPP1 in cancer has been reported in several studies 21,22,25,[42][43][44] . However, the relationship between ASPP1 and metastasis has never been reported in CRC.…”

Section: Discussionmentioning

confidence: 99%

“…High ASPP2/low iASPP expression in a number of human cancers has been evaluated and found to correlate with higher survival rates, improved curative effect and better prognosis [17][18][19][20][21][22] . Meanwhile, ASPP1 has been found to be downregulated in a variety of human cancers including acute lymphoblastic leukemia, breast cancer, hepatitis B virus-positive hepatocellular carcinoma, clear cell renal cell carcinoma and colorectal cancer (CRC) [21][22][23][24][25] . Previously, we have demonstrated that ASPP2 downregulation can promote invasion and migration by controlling β-catenin-dependent regulation of ZEB1 26 ; however, the mechanisms underlying ASPP1's functions in CRC remain unclear.…”

Section: Introductionmentioning

confidence: 99%

ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer

et al. 2020

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The apoptosis-stimulating protein of p53 (ASPP) family of proteins can regulate apoptosis by interacting with the p53 family and have been identified to play an important role in cancer progression. Previously, we have demonstrated that ASPP2 downregulation can promote invasion and migration by controlling β-catenin-dependent regulation of ZEB1, however, the role of ASPP1 in colorectal cancer (CRC) remains unclear. We analyzed data from The Cancer Genome Atlas (TCGA) and coupled this to in vitro experiments in CRC cell lines as well as to experimental pulmonary metastasis in vivo. Tissue microarrays of CRC patients with information of clinical-pathological parameters were also used to investigate the expression and function of ASPP1 in CRC. Here, we report that loss of ASPP1 is capable of enhancing migration and invasion in CRC, both in vivo and in vitro. We demonstrate that depletion of ASPP1 could activate expression of Snail2 via the NF-κB pathway and in turn, induce EMT; and this process is further exacerbated in RAS-mutated CRC. ASPP1 could be a prognostic factor in CRC, and the use of NF-κB inhibitors may provide new strategies for therapy against metastasis in ASPP1-depleted CRC patients.

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The family of apoptosis-stimulating proteins of p53 is dysregulated in colorectal cancer patients

Cited by 12 publications

References 42 publications

Melittin suppresses growth and induces apoptosis of non-small-cell lung cancer cells via down-regulation of TGF-β-mediated ERK signal pathway

Melittin suppresses growth and induces apoptosis of non-small-cell lung cancer cells via down-regulation of TGF-β-mediated ERK signal pathway

iASPP mediates p53 selectivity through a modular mechanism fine-tuning DNA recognition

ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer

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