Non-canonical Fzd7 signaling contributes to breast cancer mesenchymal-like stemness involving Col6a1

Yin, Ping; Bai, Yu; Wang, Zhuo; Sun, Yu; Gao, Jian; Lei, Na; Zhang, Zhongbo; Wang, Wei; Zhao, Chenghai

doi:10.1186/s12964-020-00646-2

Cited by 17 publications

(14 citation statements)

References 38 publications

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“…In contrast, fluorescence recovery after photobleaching (FRAP) revealed that WNT5B did not affect FZD6 mobility, suggesting a lack of WNT5B-FZD6 interactions, at least in the HEK293T model system ( Kilander et al, 2014 ). In silico analysis predicts that FZD8 has the highest affinity ( Agostino et al, 2017 ; Dahiya et al, 2019 ), while in vitro and in vivo studies show that WNT5B can bind to FZD1 ( Park et al, 2015 ), FZD2 ( van Dijk et al, 2016 ), FZD4 ( Mazzotta et al, 2016 ; Sarin et al, 2018 ), FZD5 ( Sarin et al, 2018 ), FZD6 ( Katanaev and Buestorf, 2009 ; Mazzotta et al, 2016 ), and FZD7 ( Yin et al, 2020 ).…”

Section: Wnt5b Activity and Signalingmentioning

confidence: 99%

WNT5B in Physiology and Disease

Suthon

Perkins

Bryja

et al. 2021

Front. Cell Dev. Biol.

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WNT5B, a member of the WNT family of proteins that is closely related to WNT5A, is required for cell migration, cell proliferation, or cell differentiation in many cell types. WNT5B signals through the non-canonical β-catenin-independent signaling pathway and often functions as an antagonist of canonical WNT signaling. Although WNT5B has a high amino acid identity with WNT5A and is often assumed to have similar activities, WNT5B often exhibits unique expression patterns and functions. Here, we describe the distinct effects and mechanisms of WNT5B on development, bone, adipose tissue, cardiac tissue, the nervous system, the mammary gland, the lung and hematopoietic cells, compared to WNT5A. We also highlight aberrances in non-canonical WNT5B signaling contributing to diseases such as osteoarthritis, osteoporosis, obesity, type 2 diabetes mellitus, neuropathology, and chronic diseases associated with aging, as well as various cancers.

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Section: Wnt5b Activity and Signalingmentioning

confidence: 99%

WNT5B in Physiology and Disease

Suthon

Perkins

Bryja

et al. 2021

Front. Cell Dev. Biol.

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“…In ovarian cancer, FZD7 expression correlated with resistance to platinum-based chemotherapy, tumor initiation, and cancer stem cell (CSC) proliferation (55,56). In additional examples, FZD7 was associated with epithelial-mesenchymal transition in triple-negative breast cancer (57), cisplatin and paclitaxel resistance in uterine cancer (58), and tumor proliferation in on October 24, 2021. © 2021 American Association for Cancer Research.…”

Section: Discussionmentioning

confidence: 99%

A FZD7-specific Antibody–Drug Conjugate Induces Ovarian Tumor Regression in Preclinical Models

Sonavane

et al. 2021

Molecular Cancer Therapeutics

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Though WNT signaling is frequently dysregulated in solid tumors, drugging this pathway has been challenging due to off-tumor effects. Current clinical pan-WNT inhibitors are non-specific and lead to adverse effects, highlighting the urgent need for more specific WNT-pathway targeting strategies. We identified elevated expression of the WNT receptor Frizzled class receptor 7 (FZD7) in multiple solid cancers in The Cancer Genome Atlas, particularly in the mesenchymal and proliferative subtypes of ovarian serous cystadenocarcinoma, which correlate with poorer median patient survival. Moreover, we observed increased FZD7 protein expression in ovarian tumors compared to normal ovarian tissue, indicating that FZD7 may be a tumorspecific antigen. We therefore developed a novel antibody-drug conjugate, septuximab vedotin (F7-ADC), which is composed of a chimeric human-mouse antibody to human FZD7 conjugated to the microtubule-inhibiting drug monomethyl auristatin E (MMAE). F7-ADC selectively binds human FZD7, potently kills ovarian cancer cells in vitro, and induces regression of ovarian tumor xenografts in murine models. To evaluate F7-ADC toxicity in vivo, we generated mice harboring a modified Fzd7 gene where the resulting Fzd7 protein is reactive with the humantargeting F7-ADC. F7-ADC treatment of these mice did not induce acute toxicities, indicating a potentially favorable safety profile in patients. Overall, our data suggest that the antibody-drug conjugate approach may be a powerful strategy to combat FZD7-expressing ovarian cancers in the clinic.

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“…Since the end of 1970s, its incidence ranks the first place of female tumors, and it increases by 2% per year [ 19 ]. Advanced breast cancer is prone to distal metastasis, which greatly increases the difficulty of treatment [ 20 ]. Conventional surgical resection and chemoradiotherapy have little effect on breast cancer with high metastasis [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Tetraspanin 1 (TSPAN1) promotes growth and transferation of breast cancer cells via mediating PI3K/Akt pathway

Chen

Gong

et al. 2021

Bioengineered

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The incidence and mortality of breast cancer rank first among all types of female tumors. To improve patients’ prognosis with advanced breast cancer, new and more effective targets still need to be explored and identified. Tetraspanin 1 (TSPAN1) is highly expressed in several cancers and affects the progression of these tumors. However, there are few studies focused on its role in breast cancer. Previous study showed that TSPAN1 promoted epithelial-mesenchymal transition (EMT) and metastasis, and whether TSPAN1 could promote breast cancer via regulating EMT needs further study. In this study, we found high TSPAN1 expression in breast cancer tumor samples and cell lines which was confirmed by bioinformation analysis. The ablation of TSPAN1 suppressed the growth, and motility of breast cancer cells. We further found that TSPAN1 affected the EMT and mediated the PI3K/Akt pathway in breast cancer cells. In addition, TSPAN1 depletion suppressed tumor growth of breast cancer in mice. In summary, we thought TSPAN1 suppressed growth and motility of breast cancer via mediating EMT and PI3K/AKT pathway, and could serve as a potential target for treatment of breast cancer.

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Non-canonical Fzd7 signaling contributes to breast cancer mesenchymal-like stemness involving Col6a1

Cited by 17 publications

References 38 publications

WNT5B in Physiology and Disease

WNT5B in Physiology and Disease

A FZD7-specific Antibody–Drug Conjugate Induces Ovarian Tumor Regression in Preclinical Models

Tetraspanin 1 (TSPAN1) promotes growth and transferation of breast cancer cells via mediating PI3K/Akt pathway

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