Related Experiment Video
Updated: Jun 1, 2026
06:09
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
RASSF1A suppresses melanoma development by modulating apoptosis and cell-cycle progression
Mei Yi1, Jianbo Yang, Xiang Chen
1Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Journal of Cellular Physiology
|June 11, 2011
Summary
The Ras association domain family 1, isoform A (RASSF1A) gene, a tumor suppressor, is down-regulated in melanoma. Restoring RASSF1A inhibits melanoma growth and metastasis by affecting cell cycle and apoptosis.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Ras association domain family 1, isoform A (RASSF1A) is a tumor suppressor gene.
- RASSF1A down-regulation via promoter hypermethylation is common in malignant melanoma.
- RASSF1A's role in melanoma development and its molecular mechanisms require further investigation.
Purpose of the Study:
- To investigate the biological functions of RASSF1A in melanoma.
- To elucidate the molecular mechanisms underlying RASSF1A's tumor suppressor activity in melanoma.
- To identify potential diagnostic and therapeutic targets for melanoma.
Main Methods:
- Comparative analysis of RASSF1A expression in melanoma tissues, cell lines, and normal melanocytes.
- Ectopic expression of RASSF1A in a RASSF1A-deficient melanoma cell line (A375).
- In vitro assays for cell viability, cell-cycle progression, and apoptosis.
- In vivo tumorigenicity assays in nude mice.
- Gene expression profiling and analysis of signaling pathways (ASK1/p38 MAPK, Akt/p70S6K/eIF4E).
Main Results:
- RASSF1A is down-regulated in melanoma tissues and cell lines, correlating negatively with lymph node metastasis.
- Ectopic RASSF1A expression reduced cell viability, suppressed cell-cycle progression, and enhanced apoptosis in A375 cells.
- In vivo, RASSF1A inhibited tumor growth in nude mice, associated with decreased proliferation and increased apoptosis.
- RASSF1A modulated the expression of 209 genes and activated the ASK1/p38 MAPK pathway for apoptosis, while inhibiting the Akt/p70S6K/eIF4E pathway.
Conclusions:
- RASSF1A functions as a tumor suppressor in melanoma by inhibiting cell proliferation, migration, and promoting apoptosis.
- RASSF1A exerts its effects through modulation of specific gene expression and signaling pathways, including ASK1/p38 MAPK and Akt/p70S6K/eIF4E.
- RASSF1A represents a potential therapeutic target for melanoma treatment.
Related Concept Videos
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
02:38The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
03:03mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...