<p>ADAMTS8 Inhibits Cell Proliferation and Invasion, and Induces Apoptosis in Breast Cancer</p>

Abstract

Introduction: A disintegrin and metallopeptidase with thrombospondin motifs (ADAMTSs), whose expression is dysregulated in various cancers, is implicated in cancer development. Herein, we aimed to investigate the functional role of ADAMTS8 in breast cancer (BC) and explore the underlying mechanisms. Methods: The protein expression of ADAMTS8 in BC cell lines and tumor tissues from BC patients was quantified by Western blot. ADAMTS8 overexpression was induced by transfection with pEZ-M90-ADAMTS8 plasmid using lipofectamine 2000. To generate ADAMTS8 stable knockdown cells, MDA-MB-231 cells were transfected with psi-H1-ADAMTS8siRNA plasmids. Cell counting kit-8 (CCK-8) assay, wound-healing assay, transwell assay and flow cytometry assay were employed to analyze the effects of ADAMTS8 on the proliferation, migration, invasion and apoptosis of BC cells. Chemosensitivity also was assessed using CCK-8 assay. The expressions of β-catenin, MMP-7 and c-Myc were measured by Western blot. Results: Our results showed that ADAMTS8 expression was significantly lower in BC tissues than that in adjacent non-tumor tissues. Overexpression of ADAMTS8 in MDA-MB-453 cells could inhibit the cell proliferation, migration and invasion and promote apoptosis. ADAMTS8 knockdown displayed the reverse effect in MDA-MB-231 cells. Consistently, in vivo data showed that ADAMTS8 overexpression led to a reduction in tumor growth. In addition, chemosensitivity testing in MDA-MB-453 cells transfected with pEZ-M90-ADAMTS8 plasmid indicated that cisplatin inhibited cell growth dramatically. Furthermore, attenuated β-catenin, MMP-7 and c-Myc level was detected after ADAMTS8 overexpression. Conclusion: These results indicate that increased ADAMTS8 expression could modify the progression of BC by inhibiting cell proliferation and invasion while promoting the apoptosis of BC cells. Thus, ADAMTS8 represents a potential therapeutic target for BC therapy.

The Therapeutic Potential of ADAMTS8 in Lung Adenocarcinoma without Targetable Therapy

“…When utilizing the database from the CancerSEA, we found that low levels of ADAMTS8 enabled cancer cell invasion in glioblastoma multiforme (GBM). This invasion phenotypic change was consistent with breast cancer [ 33 ]. The GSEA using the TCGA cohort also suggested that ADAMTS8 was involved in poor survival in the Shedden lung cancer cohort.…”

“…ADAMTS8 belongs to the ADAMTS family, also known as METH-2, which play roles in a wide range of physiological processes, such as cell proliferation, apoptosis, migration, invasion, angiogenesis and extracellular matrix degradation [ 32 ]. It was initially recognized as an antiangiogenic factor in a variety of diseases, such as pulmonary artery hypertension [ 32 ] and different neoplastic diseases [ 33 , 34 ]. This study utilized bulky NGS to analyze the expression of different members of the ADAMTS family from eight paired normal and tumor tissues.…”

Altered gene expression of selected matrix metalloproteinase system proteins in the broiler chicken gastrointestinal tract during post-hatch development and coccidia infection

“…There are no available reports examining the effect of Eimeria or other infections on the ADAMTS8 expression/activity in the avian intestine. This enzyme, a member of ADAMTS family, possesses anti-angiogenic properties ( Dunn et al, 2006 ) can inhibit cell proliferation, migration and invasion and promote apoptosis ( Zhao et al, 2018 ; Zhang et al, 2020 ), therefore, some alterations in ADAMTS8 mRNA expression observed in this study may be related to the modulation of mentioned processes in the intestinal sections of Eimeria -challenged chickens.…”

Establishment of a 6-signature risk model associated with cellular senescence for predicting the prognosis of breast cancer

“…ADAMTS8 is one of the ADAMTS family proteins whose structure and function are similar to the matrix metalloproteinases (MMPs). [29] The ADAMTS genes participate in a wide range of biological processes such as extracellular matrix assembly and degradation, and ADAMTS8 has been proven to function as a tumor suppressor gene for BRCA. [30] DCAF12L2 is involved in a variety of cellular processes such as cell cycle progression and apoptosis, and it was only found to correlate with the microsatellite instability in colorectal cancer [31] but no research was reported about BRCA.…”