CD147 Is a Novel Chemotherapy or Prevention Target in Melanoma

Peng, Cong; Chen, Xiang

doi:10.1016/j.jisp.2018.10.001

Cited by 4 publications

(2 citation statements)

References 33 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD147, also known as Basigin or extracellular matrix metalloproteinase inducer (EMMPRIN), is a multifunctional glycoprotein involved in various biological functions including cell proliferation, survival, and invasion, and is expressed at high levels in a variety of human cancers 10 - 13 . The N-terminal domain of CD147 contains three glycosylation sites, which results in its molecular mass ranges from 27 kDa for the non-glycosylated form (NoG-CD147) to 32 kDa for the low-glycosylated (LG-CD147) form, and 40-65 kDa for high-glycosylated CD147 (HG-CD147) according to immunoblot analysis 13 , 14 . HG-CD147 is the mature and active form for facilitating the translocation of monocarboxylate transporters MCT1 and MCT4 to the membrane 9 , 13 , 15 .…”

Section: Introductionmentioning

confidence: 99%

HSPA12A unstabilizes CD147 to inhibit lactate export and migration in human renal cell carcinoma

Min¹,

Zhang²,

Li³

et al. 2020

Theranostics

View full text Add to dashboard Cite

Background: Metastasis accounts for 90% of cancer-associated mortality in patients with renal cell carcinoma (RCC). However, the clinical management of RCC metastasis is challenging. Lactate export is known to play an important role in cancer cell migration. This study investigated the role of heat shock protein A12A (HSPA12A) in RCC migration. Methods: HSPA12A expression was examined in 82 pairs of matched RCC tumors and corresponding normal kidney tissues from patients by immunoblotting and immunofluorescence analyses. The proliferation of RCC cells was analyzed using MTT and EdU incorporation assays. The migration of RCC cells was evaluated by wound healing and Transwell migration assays. Extracellular acidification was examined using Seahorse technology. Protein stability was determined following treatment with protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132. Mass spectrometry, immunoprecipitation, and immunoblotting were employed to examine protein-protein interactions. Results: RCC tumors from patients showed downregulation of HSPA12A, which was associated with advanced tumor node metastasis stage. Intriguingly, overexpression of HSPA12A in RCC cells inhibited migration, whereas HSPA12A knockdown had the opposite effect. Lactate export, glycolysis rate, and CD147 protein abundance were also inhibited by HSPA12A overexpression but promoted by HSPA12A knockdown. An interaction of HSPA12A with HRD1 ubiquitin E3 ligase was detected in RCC cells. Further studies demonstrated that CD147 ubiquitination and proteasomal degradation were promoted by HSPA12A overexpression whereas inhibited by HSPA12A knockdown. Notably, the HSPA12A overexpression-induced inhibition of lactate export and migration were abolished by CD147 overexpression. Conclusion: Human RCC shows downregulation of HSPA12A. Overexpression of HSPA12A in RCC cells unstabilizes CD147 through increasing its ubiquitin-proteasome degradation, thereby inhibits lactate export and glycolysis, and ultimately suppresses RCC cell migration. Our results demonstrate that overexpression of HSPA12A might represent a viable strategy for managing RCC metastasis.

show abstract

Section: Introductionmentioning

confidence: 99%

HSPA12A unstabilizes CD147 to inhibit lactate export and migration in human renal cell carcinoma

Min¹,

Zhang²,

Li³

et al. 2020

Theranostics

View full text Add to dashboard Cite

show abstract

“…It has been shown that melanoma cell proliferation, migration, and metastasis decrease secondary to CD147 silencing via the regulation of MMP-2, MMP-9, and vascular endothelial growth factor. 5 Hatanaka et al used a combination therapy of epidermal growth factor receptor and CD147 inhibitors to treat BRAF-mutated malignant melanoma. 6 On the other hand, Zhao et al found that CD147 downregulation leads to the apoptosis of melanoma cells via the regulation of IGFBP2 expression in the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, and suggested CD147 as a potential target for melanoma treatment.…”

mentioning

confidence: 99%

CD147 inhibitors as a treatment for melanoma: Promising agents against SARS‐CoV ‐2 infection

Pourani

Nekooghadam

Youssefian

et al. 2020

Dermatologic Therapy

View full text Add to dashboard Cite

Dear Editor, Many people worldwide are struggling with the coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). First reported in China in December 2019, the disease soon became a pandemic. During the COVID-19 pandemic, scientists have conducted many research projects to discover optimal treatment options. 1 The CD147 protein (known as basigin) is a transmembrane protein that has recently been suggested as a potential receptor for SARS-CoV-2. This protein interacts with several extracellular and intracellular proteins such as cyclophilins A and B and matrix metallopeptidases (MMPs). 2 Recent studies have reported that the spike protein of SARS-CoV-2 attaches to host cells via angiotensinconverting enzyme-2 (ACE-2) and CD147 receptors. CD147 is should be appraised. High-quality studies concerning this therapeutic target are warranted.

show abstract