Background: Malignant melanoma is the leading cause of death among skin cancer patients due to its tendency to metastasize. Alterations at the molecular level are often evident, which is why melanoma biology has garnered increasing interest. The hedgehog (Hh) pathway, which is essential for embryonic development, is aberrantly re-activated in melanoma and may represent a promising therapeutic target. In addition, carbonic anhydrase XII (CAXII) represents a poor prognostic target for hypoxic tumors, such as melanoma, and is involved in cell migration. Thus, we decided to investigate whether and how the Hh pathway and CAXII may control melanoma cell migration and invasiveness.
Methods: The migratory and invasive capabilities of SK-MEL-28 and A375 cell lines, either un-transfected or transiently transfected with Smoothened (SMO), GLI1, or CAXII siRNA, were studied under normoxic or hypoxic conditions.
Results: For the first time, we showed that SMO and GLI1 silencing resulted in the downregulation of CAXII expression in both moderately and highly invasive melanoma cells under hypoxia. The Hh pathway as well as CAXII inhibition by siRNA resulted in impaired malignant melanoma migration and invasion.
Conclusion: Our results suggest that CAXII and the Hh pathway are relevant in melanoma invasion and may be novel and promising therapeutical targets for melanoma clinical management.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9563772 | PMC |
| http://dx.doi.org/10.3390/cancers14194776 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Structure-guided identification of mitogen-activated protein kinase-1 inhibitors towards anticancer therapeutics.
PLoS One
January 2025
Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.
Mitogen-activated protein kinase 1 (MAPK1) is a serine/threonine kinase that plays a crucial role in the MAP kinase signaling transduction pathway. This pathway plays a crucial role in various cellular processes, including cell proliferation, differentiation, adhesion, migration, and survival. Besides, many chemotherapeutic drugs targeting the MAPK pathway are used in clinical practice, and novel inhibitors of MAPK1 with improved specificity and efficacy are required.
View Article and Find Full Text PDFExtracellular vesicle-associated miR-ERIA exerts the anti-angiogenic effect of macrophages in diabetic wound healing.
Diabetes
January 2025
Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Many cell types are involved in the regulation of cutaneous wound healing in diabetes. Clarifying the mechanism of cell-cell interactions is important for identifying therapeutic targets for diabetic cutaneous ulcers. The function of vascular endothelial cells in the cutaneous microenvironment is critical, and a decrease in their biological function leads directly to refractory wound healing.
View Article and Find Full Text PDFERBB4 selectively amplifies TGF-β pro-metastatic responses.
Cell Rep
January 2025
MOE Key Laboratory of Biosystems Homeostasis & Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Center for Life Sciences, Shaoxing Institute, Zhejiang University, Shaoxing, Zhejiang 321000, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, China; The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, China. Electronic address:
Transforming growth factor β (TGF-β) is well known to play paradoxical roles in tumorigenesis as it has both growth-inhibitory and pro-metastatic effects. However, the underlying mechanisms of how TGF-β drives the opposing responses remain largely unknown. Here, we report that ERBB4, a member of the ERBB receptor tyrosine kinase family, specifically promotes TGF-β's metastatic response but not its anti-growth response.
View Article and Find Full Text PDFIntegrative Transcriptome-Wide Association Study With Expression Quantitative Trait Loci Colocalization Identifies a Causal VAMP8 Variant for Nasopharyngeal Carcinoma Susceptibility.
Adv Sci (Weinh)
January 2025
State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, P. R. China.
Nasopharyngeal carcinoma (NPC) is an Asia-prevalent malignancy, yet its genetic underpinnings remain incompletely understood. Here, a transcriptome-wide association study (TWAS) is conducted on NPC, leveraging gene expression prediction models based on epithelial tissues and genome-wide association study (GWAS) summary statistics from 1577 NPC cases and 6359 controls of southern Chinese descent. The TWAS identifies VAMP8 on chromosome 2p11.
View Article and Find Full Text PDFEffect of human myoblasts on tenogenic progression in 2D and 3D culture models.
J Anat
January 2025
Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Copenhagen University Hospital - Bispebjerg-Frederiksberg, Copenhagen, Denmark.
Tendon injuries and disorders associated with mechanical tendon overuse are common musculoskeletal problems. Even though tendons play a central role in human movement, the intrinsic healing process of tendon is very slow. So far, it is known that tendon cell activity is supported by several interstitial cells within the tendon.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!