BMP signaling is a therapeutic target in ovarian cancer

Fukuda, Tomohiko; Fukuda, Ryoko; Tanabe, Ryo; Koinuma, Daizo; Koyama, Hiroo; Hashizume, Yoshinobu; Moustakas, Aristidis; Miyazono, Kohei; Heldin, Carl‐Henrik

doi:10.1038/s41420-020-00377-w

Cited by 27 publications

(54 citation statements)

References 47 publications

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“…In accordance with this, BMP2 clearly induced SMAD1/5/8 phosphorylation and ID1 expression in Ishikawa cells; LDN193189 inhibited these effects. We previously reported that BMP2 also increased sphere formation and migration of ovarian cancer cells [17]. Considering that the expression patterns of BMP receptors were similar between EC and ovarian cancer cells [17], they may share a common response to BMP2 stimulation.…”

Section: Discussionmentioning

confidence: 83%

“…We previously reported that BMP2 also increased sphere formation and migration of ovarian cancer cells [17]. Considering that the expression patterns of BMP receptors were similar between EC and ovarian cancer cells [17], they may share a common response to BMP2 stimulation.…”

Section: Discussionmentioning

confidence: 83%

“…In addition, mRNAs of BMP ligands and receptors are over-expressed in EC. Overexpression of BMP ligands and receptors is also found in ovarian cancer [17]. Furthermore, high BMPR2 mRNA expression correlates with poor prognosis in ovarian cancer [17].…”

Section: Discussionmentioning

confidence: 99%

“…RNA extraction, cDNA synthesis, and real-time RT-PCR fluorescence detection were performed as previously described [17]. Primers for each gene are listed in Table S2.…”

Section: Rna Extraction and Real-time Pcrmentioning

confidence: 99%

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Tumor Promoting Effect of BMP Signaling in Endometrial Cancer

Fukuda

Miyazono

et al. 2021

IJMS

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The effects of bone morphogenetic proteins (BMPs), members of the transforming growth factor-β (TGF-β) family, in endometrial cancer (EC) have yet to be determined. In this study, we analyzed the TCGA and MSK-IMPACT datasets and investigated the effects of BMP2 and of TWSG1, a BMP antagonist, on Ishikawa EC cells. Frequent ACVR1 mutations and high mRNA expressions of BMP ligands and receptors were observed in EC patients of the TCGA and MSK-IMPACT datasets. Ishikawa cells secreted higher amounts of BMP2 compared with ovarian cancer cell lines. Exogenous BMP2 stimulation enhanced EC cell sphere formation via c-KIT induction. BMP2 also induced EMT of EC cells, and promoted migration by induction of SLUG. The BMP receptor kinase inhibitor LDN193189 augmented the growth inhibitory effects of carboplatin. Analyses of mRNAs of several BMP antagonists revealed that TWSG1 mRNA was abundantly expressed in Ishikawa cells. TWSG1 suppressed BMP7-induced, but not BMP2-induced, EC cell sphere formation and migration. Our results suggest that BMP signaling promotes EC tumorigenesis, and that TWSG1 antagonizes BMP7 in EC. BMP signaling inhibitors, in combination with chemotherapy, might be useful in the treatment of EC patients.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

“…RNA extraction, cDNA synthesis, and real-time RT-PCR fluorescence detection were performed as previously described [17]. Primers for each gene are listed in Table S2.…”

Section: Rna Extraction and Real-time Pcrmentioning

confidence: 99%

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Tumor Promoting Effect of BMP Signaling in Endometrial Cancer

Fukuda

Miyazono

et al. 2021

IJMS

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“…BMP protein is a part of the transforming growth factor-β (TGF-β) family and plays pivotal roles in the morphogenesis of different organs, including the neural system. BMP signaling has also been reported as a tumor promoter as well as a tumor suppressor in various types of cancer [ 80 ]. Notch signaling is a conserved ligand-receptor signaling pathway that is involved in fundamental mechanistic functions, such as cell survival, differentiation, development, and apoptosis.…”

Section: Lncrnas In Signaling Pathways and Brain Tumorsmentioning

confidence: 99%

Long non-coding RNAs in brain tumors: roles and potential as therapeutic targets

et al. 2021

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Brain tumors are associated with adverse outcomes despite improvements in radiation therapy, chemotherapy, and photodynamic therapy. However, treatment approaches are evolving, and new biological phenomena are being explored to identify the appropriate treatment of brain tumors. Long non-coding RNAs (lncRNAs), a type of non-coding RNA longer than 200 nucleotides, regulate gene expression at the transcriptional, post-transcriptional, and epigenetic levels and are involved in a variety of biological functions. Recent studies on lncRNAs have revealed their aberrant expression in various cancers, with distinct expression patterns associated with their instrumental roles in cancer. Abnormal expression of lncRNAs has also been identified in brain tumors. Here, we review the potential roles of lncRNAs and their biological functions in the context of brain tumors. We also summarize the current understanding of the molecular mechanisms and signaling pathways related to lncRNAs that may guide clinical trials for brain tumor therapy.

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