Related Experiment Video

Updated: Oct 26, 2025

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

9.1K

ANXA10 promotes melanoma metastasis by suppressing E3 ligase TRIM41-directed PKD1 degradation

Xuerui Zhang1, Zhaoqing Hu2, Xinran Wang2

  • 1The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China; Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc., Changzhou, China.

Cancer Letters
|July 29, 2021
PubMed

Insights

Annexin A10 (ANXA10) drives melanoma metastasis by inhibiting SMAD6. Blocking this ANXA10-PKD1-SMAD6 pathway may offer new melanoma treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Melanoma is a highly metastatic cancer requiring targeted therapies.
  • Annexin A10 (ANXA10) is implicated in tumor progression, but its role in melanoma is unclear.

Purpose of the Study:

  • To investigate the role of ANXA10 in melanoma progression and metastasis.
  • To elucidate the molecular mechanisms underlying ANXA10's function in melanoma.

Main Methods:

  • ANXA10 knockout in melanoma cells.
  • Analysis of cell migration and metastatic activity.
  • Investigation of the TGF-β/SMAD pathway, including SMAD6, PKD1, and TRIM41 interactions.
  • Correlation analysis in melanoma cell lines and clinical samples.

Main Results:

  • ANXA10 expression is upregulated and correlates with melanoma progression.
  • ANXA10 knockout significantly reduces melanoma cell migration and metastasis.
  • ANXA10 knockout induces an N- to E-cadherin switch via SMAD6 upregulation.
  • ANXA10 interacts with PKD1, inhibiting TRIM41-mediated PKD1 degradation and thus SMAD6 suppression.

Conclusions:

  • The ANXA10-PKD1-SMAD6 axis plays a critical role in melanoma metastasis.
  • Targeting this axis presents a potential therapeutic strategy for melanoma treatment.
Keywords:
ANXA10Cadherin switchMelanoma metastasisPKD1SMAD6

More Related Videos

Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma08:18

Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma

Published on: September 8, 2021

3.1K
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

377

Related Concept Videos

Abnormal Proliferation02:23

Abnormal 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...
4.8K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.2K
mTOR Signaling and Cancer Progression03:03

mTOR 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...
4.0K
The Intrinsic Apoptotic Pathway01:31

The 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...
7.1K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.0K
MAPK Signaling Cascades01:07

MAPK 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...
6.7K