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Targeting Tumor Microenvironment Akt Signaling Represents a Potential Therapeutic Strategy for Aggressive Thyroid

Saied Mirshahidi1,2, Isabella J Yuan3, Alfred Simental3

  • 1Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.

International Journal of Molecular Sciences
|March 29, 2023
PubMed

Insights

Tumor microenvironment stromal cells promote thyroid cancer progression by enhancing cancer stem-like cells via the PI3K/Akt pathway. Targeting Akt signaling offers a potential therapeutic strategy for aggressive thyroid cancer.

Area of Science:

  • Oncology
  • Cancer Biology
  • Molecular Medicine

Background:

  • The tumor microenvironment (TME) plays a critical role in cancer progression, yet its influence on thyroid cancer, particularly via stromal cells, remains understudied.
  • Understanding these interactions is crucial for developing novel therapeutic strategies for aggressive thyroid cancer.

Purpose of the Study:

  • To investigate the impact of TME stromal cells on cancer stem-like cells (CSCs) in thyroid cancer.
  • To elucidate the underlying molecular mechanisms, focusing on the PI3K/Akt pathway.
  • To evaluate the therapeutic potential of targeting this pathway in preclinical models and clinical samples.

Main Methods:

  • Utilized in vitro assays and xenograft models to study TME stromal cell effects on CSCs.
  • Investigated the role of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway.
  • Analyzed a clinical cohort of papillary thyroid carcinomas to correlate Akt signaling with lymph node metastasis.

Main Results:

  • TME stromal cells significantly enhance CSC self-renewal and invasiveness, primarily through the PI3K/Akt pathway.
  • Disrupting Akt signaling reduced CSC aggressiveness in vitro and suppressed tumor growth and metastasis in vivo.
  • Elevated Akt signaling in clinical samples correlated with lymph node metastasis in papillary thyroid carcinomas.

Conclusions:

  • TME stromal cells contribute to thyroid cancer progression by activating the PI3K/Akt pathway in CSCs.
  • Targeting Akt signaling within the TME presents a promising therapeutic avenue for aggressive thyroid cancer.
  • This approach demonstrated therapeutic benefits without significant alterations in tumor histology or stromal gene expression.
Keywords:
Akt signalingcancer stem celltargeting aggressive diseasethyroid cancertumor stromal cell

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