Related Experiment Video

Updated: Jun 18, 2026

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
06:35

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth

Published on: December 22, 2020

Fibroblastic aspartoacylase suppresses TGFβ-mediated responses and cancer progression

Ianire Astobiza1,2, Catalina Capó-Serra3, Cristina Viera1

  • 1Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain.

Nature Communications
|June 16, 2026
PubMed

Insights

Aspartoacylase (ASPA) is repressed in cancer stroma, hindering fibroblast function. Restoring ASPA inhibits cancer progression by blocking Transforming Growth Factor Beta (TGFβ) signaling and pro-tumoral responses.

Area of Science:

  • Oncology
  • Cancer Biology
  • Metabolic Pathways

Background:

  • Cancer metabolic reprogramming focuses on tumor cells, neglecting stromal cell adaptations.
  • Stromal cells, including cancer-associated fibroblasts (CAFs), play crucial roles in tumor microenvironment.
  • The metabolic adaptations of stromal cells in cancer remain understudied.

Purpose of the Study:

  • To investigate the role of metabolic enzyme aspartoacylase (ASPA) in cancer stroma.
  • To elucidate the relationship between ASPA and Transforming Growth Factor Beta (TGFβ) signaling in fibroblasts.
  • To determine the prognostic value of ASPA in human cancer specimens.

Main Methods:

  • Identification of ASPA as a repressed enzyme in tumor stroma and CAFs.
  • Experimental analysis of the crosstalk between ASPA and TGFβ signaling in fibroblasts.
  • Correlation analysis of ASPA expression with TGFβ levels and clinical outcomes in human cancer samples.

Main Results:

  • ASPA is consistently repressed in tumor stroma and CAFs.
  • A reciprocal crosstalk exists: TGFβ suppresses ASPA, while ASPA restrains TGFβ-driven fibroblast activation.
  • ASPA restrains myofibroblast conversion, ECM remodeling, angiogenesis, and pro-tumoral macrophage phenotypes.
  • Low ASPA expression is a negative prognostic marker in various cancers, linked to high TGFβ signaling and aggressive tumor features.

Conclusions:

  • ASPA acts as a crucial regulator of fibroblast behavior within the tumor microenvironment.
  • ASPA functions as a gatekeeper against TGFβ-induced cancer progression.
  • Targeting ASPA or its regulatory pathways may offer novel therapeutic strategies for cancer treatment.

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