Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209.

Article  PubMed  Google Scholar 

Waks AG, Winer EP. Breast cancer treatment: a review. JAMA. 2019;321(3):288–300.

Article  CAS  PubMed  Google Scholar 

Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017;377(6):523–33.

Article  CAS  PubMed  Google Scholar 

Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im SA, Yusof MM, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817–28.

Article  PubMed  Google Scholar 

Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, et al. Sacituzumab Govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021;384(16):1529–41.

Article  CAS  PubMed  Google Scholar 

National Cancer Institute. SEER Cancer Statistics Review, 1975–2018. Bethesda, MD, https://seer.cancer.gov/csr/1975_2018/, based on November 2020 SEER data submission, posted to the SEER web site. 2021.

Cao Y, Slaney CY, Bidwell BN, Parker BS, Johnstone CN, Rautela J, et al. BMP4 inhibits breast cancer metastasis by blocking myeloid-derived suppressor cell activity. Cancer Res. 2014;74(18):5091–102.

Article  CAS  PubMed  Google Scholar 

Eckhardt BL, Cao Y, Redfern AD, Chi LH, Burrows AD, Roslan S, et al. Activation of Canonical BMP4-SMAD7 signaling suppresses breast cancer metastasis. Cancer Res. 2020;80(6):1304–15.

Article  CAS  PubMed  Google Scholar 

Salazar VS, Gamer LW, Rosen V. BMP signalling in skeletal development, disease and repair. Nat Rev Endocrinol. 2016;12(4):203–21.

Article  CAS  PubMed  Google Scholar 

Owens P, Pickup MW, Novitskiy SV, Chytil A, Gorska AE, Aakre ME, et al. Disruption of bone morphogenetic protein receptor 2 (BMPR2) in mammary tumors promotes metastases through cell autonomous and paracrine mediators. Proc Natl Acad Sci U S A. 2012;109(8):2814–9.

Article  CAS  PubMed  Google Scholar 

Vollaire J, Machuca-Gayet I, Lavaud J, Bellanger A, Bouazza L, El Moghrabi S, et al. The bone morphogenetic protein signaling inhibitor LDN-193189 enhances metastasis development in mice. Front Pharmacol. 2019;10:667.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pickup MW, Hover LD, Guo Y, Gorska AE, Chytil A, Novitskiy SV, et al. Deletion of the BMP receptor BMPR1a impairs mammary tumor formation and metastasis. Oncotarget. 2015;6(26):22890–904.

Article  PubMed  PubMed Central  Google Scholar 

Ampuja M, Alarmo EL, Owens P, Havunen R, Gorska AE, Moses HL, et al. The impact of bone morphogenetic protein 4 (BMP4) on breast cancer metastasis in a mouse xenograft model. Cancer Lett. 2016;375(2):238–44.

Article  CAS  PubMed  Google Scholar 

Shee K, Jiang A, Varn FS, Liu S, Traphagen NA, Owens P, et al. Cytokine sensitivity screening highlights BMP4 pathway signaling as a therapeutic opportunity in ER(+) breast cancer. FASEB J. 2019;33(2):1644–57.

Article  CAS  PubMed  Google Scholar 

Kallioniemi A. Bone morphogenetic protein 4-a fascinating regulator of cancer cell behavior. Cancer Genet. 2012;205(6):267–77.

Article  CAS  PubMed  Google Scholar 

Deng G, Chen Y, Guo C, Yin L, Han Y, Li Y, et al. BMP4 promotes the metastasis of gastric cancer by inducing epithelial-mesenchymal transition via ID1. J Cell Sci. 2020;133(11):jcs237222.

Article  CAS  PubMed  Google Scholar 

Kim JS, Kurie JM, Ahn YH. BMP4 depletion by miR-200 inhibits tumorigenesis and metastasis of lung adenocarcinoma cells. Mol Cancer. 2015;14:173.

Article  PubMed  PubMed Central  Google Scholar 

Zeng S, Zhang Y, Ma J, Deng G, Qu Y, Guo C, et al. BMP4 promotes metastasis of hepatocellular carcinoma by an induction of epithelial-mesenchymal transition via upregulating ID2. Cancer Lett. 2017;390:67–76.

Article  CAS  PubMed  Google Scholar 

Chi LH, Burrows AD, Anderson RL. Bone morphogenetic protein signaling in breast cancer progression. Growth Factors. 2019;37(1–2):12–28.

Article  CAS  PubMed  Google Scholar 

Katagiri T, Imada M, Yanai T, Suda T, Takahashi N, Kamijo R. Identification of a BMP-responsive element in Id1, the gene for inhibition of myogenesis. Genes Cells. 2002;7(9):949–60.

Article  CAS  PubMed  Google Scholar 

Lagna G, Hata A, Hemmati-Brivanlou A, Massague J. Partnership between DPC4 and SMAD proteins in TGF-beta signalling pathways. Nature. 1996;383(6603):832–6.

Article  CAS  PubMed  Google Scholar 

Hahn SA, Schutte M, Hoque AT, Moskaluk CA, da Costa LT, Rozenblum E, et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science. 1996;271(5247):350–3.

Article  CAS  PubMed  Google Scholar 

Yokoyama Y, Watanabe T, Tamura Y, Hashizume Y, Miyazono K, Ehata S. Autocrine BMP-4 signaling is a therapeutic target in colorectal cancer. Cancer Res. 2017;77(15):4026–38.

Article  CAS  PubMed  Google Scholar 

Russell R, Perkhofer L, Liebau S, Lin Q, Lechel A, Feld FM, et al. Loss of ATM accelerates pancreatic cancer formation and epithelial-mesenchymal transition. Nat Commun. 2015;6(1):7677.

Article  CAS  PubMed  Google Scholar 

Sanchez-Vega F, Mina M, Armenia J, Chatila WK, Luna A, La KC, et al. Oncogenic signaling pathways in the cancer genome atlas. Cell. 2018;173(2):321-37 e10.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jeffery TK, Upton PD, Trembath RC, Morrell NW. BMP4 inhibits proliferation and promotes myocyte differentiation of lung fibroblasts via Smad1 and JNK pathways. Am J Physiol Lung Cell Mol Physiol. 2005;288(2):L370–8.

Article  CAS  PubMed  Google Scholar 

Zhang Y, Wang Y, Yang K, Tian L, Fu X, Wang Y, et al. BMP4 increases the expression of TRPC and basal [Ca2+]i via the p38MAPK and ERK1/2 pathways independent of BMPRII in PASMCs. Plos One. 2014;9(12):e112695.

Article  PubMed  PubMed Central  Google Scholar 

Shim JH, Greenblatt MB, Xie M, Schneider MD, Zou W, Zhai B, et al. TAK1 is an essential regulator of BMP signalling in cartilage. EMBO J. 2009;28(14):2028–41.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yamaguchi K, Shirakabe K, Shibuya H, Irie K, Oishi I, Ueno N, et al. Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction. Science. 1995;270(5244):2008–11.

Article  CAS  PubMed  Google Scholar 

Chang XZ, Li DQ, Hou YF, Wu J, Lu JS, Di GH, et al. Identification of the functional role of AF1Q in the progression of breast cancer. Breast Cancer Res Treat. 2008;111(1):65–78.

Article  CAS  PubMed  Google Scholar 

Lelekakis M, Moseley JM, Martin TJ, Hards D, Williams E, Ho P, et al. A novel orthotopic model of breast cancer metastasis to bone. Clin Exp Metastasis. 1999;17(2):163–70.

Article  CAS  PubMed  Google Scholar 

Hayer A, Shao L, Chung M, Joubert LM, Yang HW, Tsai FC, et al. Engulfed cadherin fingers are polarized junctional structures between collectively migrating endothelial cells. Nat Cell Biol. 2016;18(12):1311–23.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stewart SA, Dykxhoorn DM, Palliser D, Mizuno H, Yu EY, An DS, et al. Lentivirus-delivered stable gene silencing by RNAi in primary cells. RNA. 2003;9(4):493–501.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vichai V, Kirtikara K. Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat Protoc. 2006;1(3):1112–6.

Article  CAS  PubMed  Google Scholar 

Andrews S. FastQC: a quality control tool for high throughput sequence data, v0.11.9 2020 [Available from: https://www.bioinformatics.babraham.ac.uk/projects/fastqc/.

Law CW, Alhamdoosh M, Su S, Dong X, Tian L, Smyth GK, et al. RNA-seq analysis is easy as 1–2–3 with limma Glimma and edgeR. F1000Res. 2016;5:1408.

Article  Google Scholar 

Liao Y, Smyth GK, Shi W. The R package Rsubread is easier, faster, cheaper and better for alignment and quantification of RNA sequencing reads. Nucleic Acids Res. 2019;47(8): e47.

Article  CAS  PubMed