Targeting GRP78-dependent AR-V7 protein degradation overcomes castration-resistance in prostate cancer therapy

Liao, Yuning; Liu, Yuan; Xia, Xiaohong; Shao, Zhenlong; Huang, Chuyi; He, Jinchan; Jiang, Lili; Tang, Daolin; Liu, Jinbao; Huang, Hongbiao

doi:10.7150/thno.41849

Cited by 54 publications

(55 citation statements)

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“…Studies have been demonstrated that L-THP shows a protective role in cardio, blood vessels and neural tissues via anti-apoptosis, anti-oxidant and anti-inflammation [16][17][18]. As previously reported, natural alkaloids have also been shown their brilliant anti-cancer activities in some human cancers, such as leukemia and prostate cancer [19,20]. The alkaloids can induce cell apoptosis and cell cycle arrest by interacting with DNA in vitro or inhibiting G2/M transition [20,21].…”

Section: Ivyspringmentioning

confidence: 80%

“…As previously reported, natural alkaloids have also been shown their brilliant anti-cancer activities in some human cancers, such as leukemia and prostate cancer [19,20]. The alkaloids can induce cell apoptosis and cell cycle arrest by interacting with DNA in vitro or inhibiting G2/M transition [20,21]. Considering that L-THP is an isoquinoline alkaloid, some researchers explore the potential effect against cancers.…”

Section: Ivyspringmentioning

confidence: 98%

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Targeting ERα degradation by L-Tetrahydropalmatine provides a novel strategy for breast cancer treatment

Xia¹,

He²,

Liu³

et al. 2020

Int. J. Biol. Sci.

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The incidence and mortality of breast cancer (BCa) are the highest among female cancers. There are approximate 70% BCa that are classified as estrogen receptor alpha (ERα) positive. Therefore, targeting ERα is the most significantly therapeutic schedule. However, patients with breast cancer develop resistance to ERα or estrogen (E2) antagonists such as fulvestrant and tamoxifen. In the present study, we found that L-Tetrahydropalmatine (L-THP) significantly suppressed cell proliferation in ERα + BCa cells via inducing cell cycle arrest rather than apoptosis. Additionally, L-THP enhanced the sensitivity of ERα + BCa cells to tamoxifen and fulvestrant. Mechanically, the application of L-THP promotes ERα degradation through accumulating ubiquitin chains on ERα. Overexpressing ERα abrogates L-THP induced-antiproliferation in ERα + BCa cells. Collectively, our work indicates that L-THP may represent a potentially novel therapeutic medicine for ERα + breast cancer patient.

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Section: Ivyspringmentioning

confidence: 80%

Section: Ivyspringmentioning

confidence: 98%

Targeting ERα degradation by L-Tetrahydropalmatine provides a novel strategy for breast cancer treatment

Xia¹,

He²,

Liu³

et al. 2020

Int. J. Biol. Sci.

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“…Total lysates were harvested, followed by SDS-PAGE. For protein interaction (co-IP) analysis, reported in our previous study 38,39 , antibodies and dynabeads were mixtured for 16-24 h. Cell lysates from cells were used to react with the mixture of antibodies and dynabeads, and rotated for 1 h. The mixtures were washed with PBS-T and then loading buffer was used to suspended, followed by western blot.…”

Section: Western Blot and Co-ip Assaymentioning

confidence: 99%

Deubiquitination of CD36 by UCHL1 promotes foam cell formation

Xia

Liu

et al. 2020

Cell Death Dis

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Atherosclerosis-associated cardiovascular diseases are main causes leading to high mortality worldwide. Macrophagederived foam cell formation via uptaking modified lipoproteins is the initial and core step in the process of atherosclerosis. Meanwhile, scavenger receptor is indispensable for the formation of foam cells. UCHL1, a deubiquitinase, has been widely studied in multiple cancers. UCHL1 could be an oncogene or a tumor suppressor in dependent of tumor types. It remains unknown whether UCHL1 influences cellular oxLDL uptake. Herein we show that UCHL1 deletion significantly inhibits lipid accumulation and foam cell formation. Subsequently, we found that UCHL1 inhibitor or siRNA downregulates the expression of CD36 protein whereas SR-A, ABCA1, ABCG1, Lox-1, and SR-B1 have no significant change. Furthermore, the treatment of UCHL1 inhibition increases the abundance of K48-polyubiquitin on CD36 and the suppression of lipid uptake induced by UCHL1 deficiency is attenuated by blocking CD36 activation. Our study concluded that UCHL1 deletion decreases foam cell formation by promoting the degradation of CD36 protein, indicating UCHL1 may be a potential target for atherosclerosis treatment.

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“…Some proteins (such as p53, p27 and cyclins) that are involved in cell cycle regulation and tumorigenesis are specifically regulated by E3 enzymes 25 , 26 . UPS components, including three enzyme families (E1, E2, and E3) and proteasomes, are potential therapeutic targets for cancer and other diseases 20 , 27 , 28 .…”

Section: Introductionmentioning

confidence: 99%

E3 ligase ZFP91 inhibits Hepatocellular Carcinoma Metabolism Reprogramming by regulating PKM splicing

Chen

Wang

et al. 2020

Theranostics

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Rationale: Hepatocellular carcinoma (HCC) is one of the most lethal cancers, and few molecularly targeted anticancer therapies have been developed to treat it. Thus, the identification of new therapeutic targets is urgent. Metabolic reprogramming is an important hallmark of cancer. However, how ubiquitin ligases are involved in the regulation of cancer metabolism remains poorly understood. Methods: RT-PCR, western blot and IHC were used to determine ZFP91 expression. RNAi, cell proliferation, colony formation and transwell assays were used to determine the in vitro functions of ZFP91. Mouse xenograft models were used to study the in vivo effects of ZFP91. Co-IP together with mass spectrometry or western blot was utilized to investigate protein-protein interaction. Ubiquitination was analyzed using IP together with western blot. RNA splicing was assessed by using RT-PCR followed by restriction digestion. Lactate production and glucose uptake assays were used to analyze cancer metabolism. Results: We identified that an E3 ligase zinc finger protein 91 (ZFP91) suppressed HCC metabolic reprogramming, cell proliferation and metastasis in vitro and in vivo . Mechanistically, ZFP91 promoted the Lys48-linked ubiquitination of the oncoprotein hnRNP A1 at lysine 8 and proteasomal degradation, thereby inhibiting hnRNP A1-dependent PKM splicing, subsequently resulting in higher PKM1 isoform formation and lower PKM2 isoform formation and suppressing HCC glucose metabolism reprogramming, cell proliferation and metastasis. Moreover, HCC patients with lower levels of ZFP91 have poorer prognoses, and ZFP91 is an independent prognostic factor for patients with HCC. Conclusions: Our study identifies ZFP91 as a tumor suppressor of hepatocarcinogenesis and HCC metabolism reprogramming and proposes it as a novel prognostic biomarker and therapeutic target of HCC.

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Targeting GRP78-dependent AR-V7 protein degradation overcomes castration-resistance in prostate cancer therapy

Cited by 54 publications

References 1 publication

Targeting ERα degradation by L-Tetrahydropalmatine provides a novel strategy for breast cancer treatment

Targeting ERα degradation by L-Tetrahydropalmatine provides a novel strategy for breast cancer treatment

Deubiquitination of CD36 by UCHL1 promotes foam cell formation

E3 ligase ZFP91 inhibits Hepatocellular Carcinoma Metabolism Reprogramming by regulating PKM splicing

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