BMP6 Inhibits Gastric Cancer Growth and Predicts Good Prognosis

Overview

Journal J Gastrointest Oncol

Date 2024 Mar 14

PMID 38482225

Authors

Chao Song

Mengmeng Liu

Ganggang Wang

Zijin Xu

Siyang Han

Maozhen Peng

Liang Liu

Wenquan Wang

Yaolin Xu

Qianzhi Ni

Junyi He

Affiliations

Soon will be listed here.

Abstract

Background: Gastric cancer (GC) is a common tumors in the digestive tract, and effective treatment methods are still lacking. Bone morphogenetic protein 6 (BMP6) is closely related to the occurrence and development of various tumors, but its relevance to GC is still unclear. The aim of the study was to explore the relationship between BMP6 and the occurrence and development of GC.

Methods: In this study, we investigated the relationship between BMP6 and the prognosis of GC patients using bioinformatics technology and clinical tissue samples. We also explored the connection between BMP6 and the biological behavior of GC cells through molecular biology experiments and relevant animal experiments. Finally, we examined the mechanisms by which BMP6 inhibits the onset and progression of GC.

Results: Through analysis of The Cancer Genomics Atlas (TCGA) database, we observed that BMP6 is expressed at low levels in GC, and its low expression is associated with a poor prognosis in GC patients. Cell experiments demonstrated that BMP6 expression can influence the proliferation of GC cells both and . Furthermore, we discovered that BMP6 is linked to the nuclear factor-κB (NF-κB) pathway, and subsequent experiments confirmed that BMP6 can inhibit the biological activity of GC cells by activating the NF-κB pathway.

Conclusions: Our findings suggest that BMP6 is a potential prognostic biomarker in GC and can regulate the biological activity of GC cells through the NF-κB pathway. BMP6 may serve as a promising therapeutic target for GC, and our study introduces novel ideas for the prevention and treatment of this disease.

References

Li W, Ng J, Wong C, Ng E, Yu J . Molecular alterations of cancer cell and tumour microenvironment in metastatic gastric cancer. Oncogene. 2018; 37(36):4903-4920. PMC: 6127089. DOI: 10.1038/s41388-018-0341-x. View

Mo Y, Nakamura H, Tanaka T, Odani T, Perez P, Ji Y . Lysosomal exocytosis of HSP70 stimulates monocytic BMP6 expression in Sjögren's syndrome. J Clin Invest. 2022; 132(6). PMC: 8920330. DOI: 10.1172/JCI152780. View

Aqdas M, Sung M . NF-κB dynamics in the language of immune cells. Trends Immunol. 2022; 44(1):32-43. PMC: 9811507. DOI: 10.1016/j.it.2022.11.005. View

Guldenpfennig C, Teixeiro E, Daniels M . NF-kB's contribution to B cell fate decisions. Front Immunol. 2023; 14:1214095. PMC: 10391175. DOI: 10.3389/fimmu.2023.1214095. View

Xiong W, Wang L, Yu F . Expression of bone morphogenetic protein 6 in non-small cell lung cancer and its significance. Oncol Lett. 2019; 17(2):1946-1952. PMC: 6341809. DOI: 10.3892/ol.2018.9781. View

Pizzamiglio S, De Bortoli M, Taverna E, Signore M, Veneroni S, Cho W . Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors. Int J Mol Sci. 2017; 18(2). PMC: 5343944. DOI: 10.3390/ijms18020410. View

Mantziari S, St Amour P, Abboretti F, Teixeira-Farinha H, Gaspar Figueiredo S, Gronnier C . A Comprehensive Review of Prognostic Factors in Patients with Gastric Adenocarcinoma. Cancers (Basel). 2023; 15(5). PMC: 10000968. DOI: 10.3390/cancers15051628. View

Luo X, Wang G, Wang Y, Wang M, Tan Z, Luo M . Gibberellin derivative GA-13315 overcomes multidrug resistance in breast cancer by up-regulating BMP6 expression. Front Pharmacol. 2022; 13:1059365. PMC: 9748619. DOI: 10.3389/fphar.2022.1059365. View

Min D, Byun J, Lee E, Khan A, Liu C, Loudig O . Epigenetic Silencing of BMP6 by the SIN3A-HDAC1/2 Repressor Complex Drives Melanoma Metastasis via FAM83G/PAWS1. Mol Cancer Res. 2021; 20(2):217-230. PMC: 9744461. DOI: 10.1158/1541-7786.MCR-21-0289. View

10.

Wang M, Chen Y, Xu H, Zhan J, Suo D, Wang J . HKDC1 upregulation promotes glycolysis and disease progression, and confers chemoresistance onto gastric cancer. Cancer Sci. 2022; 114(4):1365-1377. PMC: 10067396. DOI: 10.1111/cas.15692. View

11.

He Y, Cui Y, Xu B, Gu J, Wang W, Luo X . Hypermethylation leads to bone morphogenetic protein 6 downregulation in hepatocellular carcinoma. PLoS One. 2014; 9(1):e87994. PMC: 3907571. DOI: 10.1371/journal.pone.0087994. View

12.

Zabkiewicz C, Resaul J, Hargest R, Jiang W, Ye L . Bone morphogenetic proteins, breast cancer, and bone metastases: striking the right balance. Endocr Relat Cancer. 2017; 24(10):R349-R366. PMC: 5574206. DOI: 10.1530/ERC-17-0139. View

13.

Ferlay J, Colombet M, Soerjomataram I, Parkin D, Pineros M, Znaor A . Cancer statistics for the year 2020: An overview. Int J Cancer. 2021; . DOI: 10.1002/ijc.33588. View

14.

Li Q, Xu X, Su D, Zhou T, Wang G, Li Z . Long-term survival of an elderly patient with advanced gastric cancer after combination therapy: a case report and literature review. BMC Cancer. 2019; 19(1):459. PMC: 6524267. DOI: 10.1186/s12885-019-5683-4. View

15.

Katsuta E, Maawy A, Yan L, Takabe K . High expression of bone morphogenetic protein (BMP) 6 and BMP7 are associated with higher immune cell infiltration and better survival in estrogen receptor‑positive breast cancer. Oncol Rep. 2019; 42(4):1413-1421. PMC: 6718975. DOI: 10.3892/or.2019.7275. View

16.

Liu G, Liu Y, Lian W, Zhao Z, Yi T, Zhou H . Reduced BMP6 expression by DNA methylation contributes to EMT and drug resistance in breast cancer cells. Oncol Rep. 2014; 32(2):581-8. DOI: 10.3892/or.2014.3224. View

17.

Wang Q, Vattai A, Vilsmaier T, Kaltofen T, Steger A, Mayr D . Immunogenomic Identification for Predicting the Prognosis of Cervical Cancer Patients. Int J Mol Sci. 2021; 22(5). PMC: 7957482. DOI: 10.3390/ijms22052442. View

18.

Silvestri L, Nai A, Dulja A, Pagani A . Hepcidin and the BMP-SMAD pathway: An unexpected liaison. Vitam Horm. 2019; 110:71-99. DOI: 10.1016/bs.vh.2019.01.004. View

19.

Gado F, Ferrario G, Della Vedova L, Zoanni B, Altomare A, Carini M . Targeting Nrf2 and NF-κB Signaling Pathways in Cancer Prevention: The Role of Apple Phytochemicals. Molecules. 2023; 28(3). PMC: 9919881. DOI: 10.3390/molecules28031356. View

20.

Zhu S, Al-Mathkour M, Cao L, Khalafi S, Chen Z, Poveda J . CDK1 bridges NF-κB and β-catenin signaling in response to H. pylori infection in gastric tumorigenesis. Cell Rep. 2023; 42(1):112005. PMC: 9973518. DOI: 10.1016/j.celrep.2023.112005. View