SCAMP3 Regulates EGFR and Promotes Proliferation and Migration of Triple-Negative Breast Cancer Cells through the

Ariana Acevedo-Díaz1, Beatriz M Morales-Cabán2, Astrid Zayas-Santiago3

  • 1Department of Biology, University of Puerto Rico, Bayamón, PR 00959, USA.

Cancers
|June 10, 2022
PubMed

Insights

Secretory carrier membrane protein 3 (SCAMP3) drives aggressive triple-negative breast cancer (TNBC) by regulating epidermal growth factor receptor (EGFR) signaling. Targeting SCAMP3 may offer a new therapeutic strategy for TNBC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options.
  • Identifying novel molecular targets is crucial for improving TNBC patient outcomes.

Purpose of the Study:

  • To investigate the role of secretory carrier membrane protein 3 (SCAMP3) in TNBC.
  • To explore the association between SCAMP3 and epidermal growth factor receptor (EGFR) in TNBC.

Main Methods:

  • Internalization assays to study SCAMP3-EGFR colocalization.
  • SCAMP3 knockout in TNBC cells to assess proliferation, migration, and invasion.
  • Immunoblotting and degradation assays to analyze EGFR regulation.
  • TNBC xenograft models and TCGA data analysis.

Main Results:

  • SCAMP3 colocalizes with and redistributes EGFR, promoting its degradation.
  • SCAMP3 depletion reduces TNBC cell proliferation, migration, and invasion.
  • SCAMP3 modulates AKT, ERK, STAT3, and PDGF signaling pathways.
  • Elevated SCAMP3 expression correlates with decreased relapse-free survival (RFS) and distant metastasis-free survival (DMFS) in TNBC patients.

Conclusions:

  • SCAMP3 plays a significant role in TNBC development and progression.
  • SCAMP3 regulates key signaling pathways implicated in cancer.
  • SCAMP3 represents a potential therapeutic target for TNBC.

Related Concept Videos

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...
4.0K
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...
3.9K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.0K
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...
6.2K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.6K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.7K