Trk Signaling Inhibition Reduces cSCC Growth and Invasion in In Vitro and Zebrafish Models and Enhances Photodynamic...

Area of Science:

• Oncology
• Dermatology
• Molecular Biology

Background:

• Cutaneous squamous cell carcinoma (cSCC) is a prevalent skin cancer with increasing incidence.
• Neurotrophins (NTs) and their receptors, like TrkA, are implicated in skin homeostasis and tumor progression.
• TrkA is highly expressed in poorly differentiated cSCC, but its functional role is underexplored.

Purpose of the Study:

• To investigate the therapeutic potential of inhibiting TrkA signaling in cSCC.
• To evaluate the effects of TrkA inhibition on cSCC cell growth, invasion, and metastasis.
• To assess TrkA inhibition in combination with photodynamic therapy.

Main Methods:

• Used a pan-Trk inhibitor (K252a) and siRNA to silence TrkA in cSCC cell lines.
• Assessed cell growth and invasion using 2D and 3D cultures in vitro.
• Evaluated tumor growth and metastasis in vivo using zebrafish xenografts.

Main Results:

• TrkA inhibition significantly reduced cSCC tumor growth and invasion, comparable to 5-FU and cisplatin.
• TrkA blockade downregulated key mitogenic and invasive markers.
• TrkA inhibition enhanced photodynamic therapy response in cSCC spheroids and reduced metastasis in zebrafish models.

Conclusions:

• TrkA is a critical regulator of cSCC survival and metastasis.
• Targeting TrkA represents a promising therapeutic strategy for cSCC, potentially enhancing existing treatments.