FBXL14 abolishes breast cancer progression by targeting CDCP1 for proteasomal degradation

Cui, Yan Hong; Kim, Hyeonmi; Lee, Minyoung; Yi, Joo Mi; Kim, Rae Kwon; Uddin, Nizam; Yoo, Kyoungkeun; Kang, Jae Hyeok; Choi, Mi Young; Cha, Hyuk‐Jin; Kwon, Ohseong; Bae, In Hwa; Kim, Min Jung; Kaushik, Neha; Lee, Su Jae

doi:10.1038/s41388-018-0372-3

Cited by 19 publications

(11 citation statements)

References 43 publications

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“…CD318 and TSPAN8 have been suggested as targets for pharmacological or antibody-driven therapies [57][58][59] . While these studies show decreased tumor growth rates or disease stabilization in vitro and in vivo, our results showed complete tumor eradication, which is most likely owed to the superior cytotoxicity of T cells representing a "living drug".…”

Section: Discussionmentioning

confidence: 99%

Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma

et al. 2021

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A major roadblock prohibiting effective cellular immunotherapy of pancreatic ductal adenocarcinoma (PDAC) is the lack of suitable tumor-specific antigens. To address this challenge, here we combine flow cytometry screenings, bioinformatic expression analyses and a cyclic immunofluorescence platform. We identify CLA, CD66c, CD318 and TSPAN8 as target candidates among 371 antigens and generate 32 CARs specific for these molecules. CAR T cell activity is evaluated in vitro based on target cell lysis, T cell activation and cytokine release. Promising constructs are evaluated in vivo. CAR T cells specific for CD66c, CD318 and TSPAN8 demonstrate efficacies ranging from stabilized disease to complete tumor eradication with CD318 followed by TSPAN8 being the most promising candidates for clinical translation based on functionality and predicted safety profiles. This study reveals potential target candidates for CAR T cell based immunotherapy of PDAC together with a functional set of CAR constructs specific for these molecules.

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Section: Discussionmentioning

confidence: 99%

Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma

et al. 2021

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“…Epitopes were retrieved with 20 mg/mL proteinase K in PBS containing 0.1% Triton X-100. Sections were incubated overnight with appropriate primary antibodies at 4°C and then processed as previously described (25).…”

Section: Ihc Analysismentioning

confidence: 99%

A Feedback Loop Comprising EGF/TGFα Sustains TFCP2-Mediated Breast Cancer Progression

et al. 2020

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Stemness and epithelial-mesenchymal transition (EMT) are two fundamental characteristics of metastasis that are controlled by diverse regulatory factors, including transcription factors. Compared with other subtypes of breast cancer, basal-type or triple-negative breast cancer (TNBC) have high frequencies of tumor relapse. However, the role of alpha-globin transcription factor CP2 (TFCP2) has not been reported as an oncogenic driver in those breast cancers. Here we show that TFCP2 is a potent factor essential for EMT, stemness, and metastasis in breast cancer. TFCP2 directly bound promoters of epidermal growth factor (EGF) and transforming growth factor alpha (TGF-α) to regulate their expression and stimulate autocrine signaling via epidermal growth factor receptor (EGFR).These findings indicate that TFCP2 is a new anti-metastatic target and reveal a novel regulatory mechanism in which a positive feedback loop comprising EGF/TGF-α and AKT can control malignant breast cancer progression. SignificanceTFCP2 is a new anti-metastatic target that controls TNBC progression via a positive feedback loop between EGF/TGF-α and the AKT signaling axis.

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“…Fbxl4 induces the ubiquitination and degradation of CUB-domain-containing protein 1 (CDCP1), a transmembrane adaptor protein, identified as a malignant prognostic marker in several types of cancers, such as acute myeloid leukemia [ 145 ]. Indeed, Fbxl14 overexpression reversed EMT by decreasing CDCP1 levels, which in consequence inhibited EMT and metastasis in in vivo breast tumor mouse models [ 86 ]. Moreover, authors described miR-17/20a as a post-transcriptional regulator of Fbxl14, thus establishing Fbxl14 as an upstream regulator of the CDCP1 pathway.…”

Section: Emt Regulation By E3 Ubiquitin-ligasesmentioning

confidence: 99%

“…Inactivated by mutation in bile duct, blood, endometrium, colon and stomach cancer. [110] Downregulated in cholangiocarcinoma [111] Fbxw1 (β-TrCP1) Expression increased in colorectal cancer [112] Fbxl5 Downregulated in gastric cancer [83] Fbxl14 Downregulated in breast cancer [86] Fbxo11…”

Section: Fbxw7mentioning

confidence: 99%

Regulation of Epithelial–Mesenchymal Plasticity by the E3 Ubiquitin-Ligases in Cancer

Rodríguez-Alonso

Casas-Pais

Roca-Lema

et al. 2020

Cancers

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The epithelial–mesenchymal plasticity (EMP) is a process by which epithelial cells acquire the ability to dynamically switch between epithelial and mesenchymal phenotypic cellular states. Epithelial cell plasticity in the context of an epithelial-to-mesenchymal transition (EMT) confers increased cell motility, invasiveness and the ability to disseminate to distant sites and form metastasis. The modulation of molecularly defined targets involved in this process has become an attractive therapeutic strategy against cancer. Protein degradation carried out by ubiquitination has gained attention as it can selectively degrade proteins of interest. In the ubiquitination reaction, the E3 ubiquitin-ligases are responsible for the specific binding of ubiquitin to a small subset of target proteins, and are considered promising anticancer drug targets. In this review, we summarize the role of the E3 ubiquitin-ligases that control targeted protein degradation in cancer-EMT, and we highlight the potential use of the E3 ubiquitin-ligases as drug targets for the development of small-molecule drugs against cancer.

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FBXL14 abolishes breast cancer progression by targeting CDCP1 for proteasomal degradation

Cited by 19 publications

References 43 publications

Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma

Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma

A Feedback Loop Comprising EGF/TGFα Sustains TFCP2-Mediated Breast Cancer Progression

Regulation of Epithelial–Mesenchymal Plasticity by the E3 Ubiquitin-Ligases in Cancer

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