Activation of TGF-β1 Pathway by SCUBE3 Regulates TWIST1 Expression and Promotes Breast Cancer Progression

Yang, Xuhui; Hu, Jingqiu; Shi, Cancan; Dai, Jun

doi:10.1089/cbr.2019.2990

Cited by 16 publications

(14 citation statements)

References 26 publications

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“…In tumours [ 14 , 20 ], SCUBE3 not only mediates the angiogenesis of lung cancer and promotes metastasis and invasion by promoting epithelial-mesenchymal transformation but also promotes the proliferation of osteosarcoma cells and influences the prognosis of patients. In a recent study [ 25 ], the expression of SCUBE3 in breast cancer cells and tissues increased significantly, and its expression was high in primary glioma specimens but low in normal brains [ 21 ]. However, the role of SCUBE3 in the proliferation of HCC cells is unclear.…”

Section: Discussionmentioning

confidence: 99%

SCUBE3 downregulation modulates hepatocellular carcinoma by inhibiting CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway

Luo

Xiong

et al. 2022

Cancer Cell Int

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Objectives We aimed to verify the role of signal peptide-CUB-EGF-like domain-containing protein3 (SCUBE3) in the hepatocellular carcinoma (HCC) progression. Methods The role of SCUBE3 in HCC cell proliferation, apoptosis, and cell cycle in vitro were detected using MTT assay, colony formation assay, 5-ethynyl-2´-deoxyuridine assay (EDU), Celigo cell counting assay, Caspase3/7 activity assay, and flow cytometry. The effect of SCUBE3 on HCC cell proliferation in vivo was inspected by a xenograft tumour model in nude mice. The related mechanisms were further studied. Results The level of SCUBE3 was upregulated in HCC tissues and cell lines. Knockdown of SCUBE3 inhibited proliferation, promoted apoptosis, and induced cell cycle arrest in HCC cell lines in vitro and in vivo. Screening of cell cycle-related proteins revealed that CCNL2, CDK6, CCNE1, and CCND1 exhibited a significantly different expression profile. We found that SCUBE3 may promote the proliferation of HCC cells by regulating CCNE1 expression. The pathway enrichment analysis showed that the TGFβ signalling pathway and the PI3K/AKT signalling pathway were significantly altered. Co-immunoprecipitation results showed that SCUBE3 binds to the TGFβRII receptor. SCUBE3 knockdown inhibited the PI3K/AKT signalling pathway and the phosphorylation of GSK3β to inhibit its kinase activity. Conclusions SCUBE3 promotes HCC development by regulating CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway. In addition, SCUBE3 may be a new molecular target for the clinical diagnosis and treatment of HCC.

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Section: Discussionmentioning

confidence: 99%

SCUBE3 downregulation modulates hepatocellular carcinoma by inhibiting CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway

Luo

Xiong

et al. 2022

Cancer Cell Int

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“…IGFBP2 overexpression is associated with breast cancer proliferation, invasion and migration [53] IGFBP2 overexpression is associated with breast cancer lymph node metastasis [54,55] induces metastatic bone colonization by endothelium recruitment through interaction with IGF type-I receptor [56] TGF-β facilitates breast cancer migration and invasion through Smad3 and ERK/Sp1 signaling pathways [57] suppresses the antitumor function of ROR1-CAR T-cells against TNBC [58] promotes breast cancer progression by TWIST expression [59] induces bone metastasis by stimulating breast cancer cells to secrete PTHrP and IL-11 [60,61] stimulates breast cancer cells to secrete PTHrP to activate osteoclasts that increase bone resorption and promote tumor cell proliferation and survival [62] Table 1. Cont.…”

Section: Igfbp2mentioning

confidence: 99%

The Role of Adipokines and Bone Marrow Adipocytes in Breast Cancer Bone Metastasis

Shin

Koo

2020

IJMS

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The morbidity and mortality of breast cancer is mostly due to a distant metastasis, especially to the bone. Many factors may be responsible for bone metastasis in breast cancer, but interactions between tumor cells and other surrounding types of cells, and cytokines secreted by both, are expected to play the most important role. Bone marrow adipocyte (BMA) is one of the cell types comprising the bone, and adipokine is one of the cytokines secreted by both breast cancer cells and BMAs. These BMAs and adipokines are known to be responsible for cancer progression, and this review is focused on how BMAs and adipokines work in the process of breast cancer bone metastasis. Their potential as suppressive targets for bone metastasis is also explored in this review.

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“…SCUBE3 promotes lung cancer cell mobility and invasiveness in vitro and tumor progression and metastasis in vivo, 179 with TGF‐β signaling induced by SCUBE3 contributing to these cancer phenotypes. More recently, TGF‐β signaling by SCUBE3 has also been implicated in the promotion of breast cancer 180 …”

Section: Tgf‐β Superfamily Co‐receptors and Their Role In Cancermentioning

confidence: 99%

“…More recently, TGF-β signaling by SCUBE3 has also been implicated in the promotion of breast cancer. 180…”

Section: Scube Proteinsmentioning

confidence: 99%

TGF‐β superfamily co‐receptors in cancer

Pawlak

Blobe

2021

Developmental Dynamics

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Transforming growth factor‐β (TGF‐β) superfamily signaling via their cognate receptors is frequently modified by TGF‐β superfamily co‐receptors. Signaling through SMAD‐mediated pathways may be enhanced or depressed depending on the specific co‐receptor and cell context. This dynamic effect on signaling is further modified by the release of many of the co‐receptors from the membrane to generate soluble forms that are often antagonistic to the membrane‐bound receptors. The co‐receptors discussed here include TβRIII (betaglycan), endoglin, BAMBI, CD109, SCUBE proteins, neuropilins, Cripto‐1, MuSK, and RGMs. Dysregulation of these co‐receptors can lead to altered TGF‐β superfamily signaling that contributes to the pathophysiology of many cancers through regulation of growth, metastatic potential, and the tumor microenvironment. Here we describe the role of several TGF‐β superfamily co‐receptors on TGF‐β superfamily signaling and the impact on cellular and physiological functions with a particular focus on cancer, including a discussion on recent pharmacological advances and potential clinical applications targeting these co‐receptors.

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Activation of TGF-β1 Pathway by SCUBE3 Regulates TWIST1 Expression and Promotes Breast Cancer Progression

Cited by 16 publications

References 26 publications

SCUBE3 downregulation modulates hepatocellular carcinoma by inhibiting CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway

SCUBE3 downregulation modulates hepatocellular carcinoma by inhibiting CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway

The Role of Adipokines and Bone Marrow Adipocytes in Breast Cancer Bone Metastasis

TGF‐β superfamily co‐receptors in cancer

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