Related Experiment Video

Updated: Feb 2, 2026

Reconstitution of Actin-Based Motility with Commercially Available Proteins
08:40

Reconstitution of Actin-Based Motility with Commercially Available Proteins

Published on: October 28, 2022

2.3K

Effects of Modulating Actin Dynamics on HER2 Cancer Cell Motility and Metastasis

Sarah Nersesian1,2, Rodette Williams1,2, Daniel Newsted1,2

  • 1Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.

Scientific Reports
|November 24, 2018
PubMed

Insights

Marine toxin mycalolide B impairs HER2-positive cancer growth and metastasis by targeting filamentous actin. Combining mycalolide B with therapies like Trastuzumab shows promise for reducing cancer spread.

Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • HER2-amplified cancers exhibit high metastatic potential.
  • Targeting cellular structures like the actin cytoskeleton presents a novel therapeutic strategy.

Purpose of the Study:

  • To investigate the efficacy of mycalolide B, a filamentous actin (F-actin) severing toxin, against HER2-positive (HER2+) cancer cells.
  • To evaluate mycalolide B in combination with Trastuzumab-emtansine (T-DM1) for enhanced anti-cancer effects.

Main Methods:

  • Treatment of HER2+ breast (HCC1954) and ovarian (SKOV3) cancer cell lines with mycalolide B.
  • Assessment of cell viability, motility, and invasion.
  • In vivo studies using SKOV3 tumor xenografts and tail vein injection models.
  • Combination therapy studies with mycalolide B and Trastuzumab or T-DM1.

Main Results:

  • Mycalolide B significantly impaired growth and viability of HER2+ cancer cells at nanomolar doses.
  • Sub-lethal mycalolide B doses inhibited cancer cell motility, invasion, and caused loss of leading edge protrusions.
  • Combination therapy with mycalolide B and Trastuzumab demonstrated maximal impairment of tumor growth and metastasis in vivo.
  • Mycalolide B reduced lung metastasis in a tail vein injection model.

Conclusions:

  • Mycalolide B effectively targets F-actin in HER2+ cancer cells, reducing their growth, motility, and metastatic potential.
  • Combination of mycalolide B with existing HER2-targeted therapies like Trastuzumab offers a promising strategy to combat metastasis in HER2+ cancers.

More Related Videos

Intracarotid Cancer Cell Injection to Produce Mouse Models of Brain Metastasis07:43

Intracarotid Cancer Cell Injection to Produce Mouse Models of Brain Metastasis

Published on: February 8, 2017

28.2K
Live Imaging of Cell Motility and Actin Cytoskeleton of Individual Neurons and Neural Crest Cells in Zebrafish Embryos10:52

Live Imaging of Cell Motility and Actin Cytoskeleton of Individual Neurons and Neural Crest Cells in Zebrafish Embryos

Published on: February 3, 2010

13.9K

Related Concept Videos

Actin Polymerization and Cell Motility01:13

Actin Polymerization and Cell Motility

Actin is a family of globular proteins that are highly abundant in eukaryotic cells. It makes up approximately 1-5% of total cell protein concentration. Actin monomers polymerize to form a complex network of polarized filaments, the actin cytoskeleton, that plays a crucial role in many cellular processes, including cell motility, division, endocytosis, and metastasis of cancer cells.
Actin cytoskeleton dynamics can produce pushing, pulling, and resistance forces that help the cell to migrate....
6.7K
Cell Motility through Blebbing01:16

Cell Motility through Blebbing

Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
2.5K
Microtubules in Cell Motility01:24

Microtubules in Cell Motility

Microtubules are thick hollow cylindrical proteins that help form the cytoskeleton. Microtubules have varied roles in the cell. These filaments help form cellular appendages like cilia and flagella, which are responsible for locomotion. The cilia arise from basal bodies, separated from the main body by a membrane-like structure forming the transition zone. This zone is the gate for the entry of lipids and proteins, creating a unique composition of lipids and proteins in the ciliary membrane and...
4.8K
The Role of Actin and Myosin in Non-muscle Cells01:10

The Role of Actin and Myosin in Non-muscle Cells

Actin and myosin or actomyosin filaments also play a significant role in cells other than those involved in muscle contraction (which occurs within the sarcomere of muscle cells). The mechanism of non-muscle cell contractile bundles was first observed in Dictyostelium and Acanthamoeba. In non-muscle cells, two bundles are commonly found: stress fibers and actomyosin adherence belts. These contractile bundles are smaller and less organized than the ones found in muscle cells. They  are held...
4.9K
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
6.6K
Actin Treadmilling01:18

Actin Treadmilling

Actin filaments undergo polymerization and depolymerization from either end. The polymerization and depolymerization rates depend on the cytosolic concentration of free G-actins. The polymerization rate is generally higher at the plus or barbed end, while the depolymerization rate is higher at the minus or pointed end. At a steady state, critical concentration describes the concentration of free G-actin monomers at which the polymerization rate at the plus end is equal to that of the...
9.7K