Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression

Goutham Venkata Naga Davuluri, Chien Chin Chen, Yen Cheng Chiu, Hung Wen Tsai, Hung Chih Chiu, Yuh Ling Chen, Pei Jane Tsai, Wan Ting Kuo, Nina Tsao, Yee Shin Lin, Chih Peng Chang

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Galectin-1 (Gal-1) is a secretory lectin with pro-tumor activities and is associated strongly with hepatocellular carcinoma (HCC) development. Although Gal-1 is a well-known soluble pro-tumor factor in the tumor microenvironment (TME), the secretion mode of Gal-1 is not clearly defined. On the other hand, in addition to cancer cells, Gal-1 is widely expressed in tumor stromal cells, including tumor-associated macrophages (TAMs). TAMs are a significant component of stromal cells in TME; however, their contributions in producing Gal-1 to TME are still not explored. Here we reveal that TAMs can actively secrete Gal-1 in response to stimuli of HCC cells. Gal-1 produced by TAMs leads to an increase of the systemic level of Gal-1 and HCC tumor growth in mice. Mechanistically, TLR2-dependent secretory autophagy is found to be responsible for Gal-1 secretion from TAMs. Gal-1 acts as a cargo of autophagosomes to fuse with multivesicular bodies via Rab11 and VAMP7-mediated vesicle trafficking before being secreted. This autophagy-regulated Gal-1 secretion in TAMs correlates to poor overall survival and progression-free survival rates of HCC patients. Our findings uncover the secretion mode of Gal-1 via secretory autophagy and highlight the pathological role of TAM-produced Gal-1 in HCC progression.

Original languageEnglish
Article number741820
JournalFrontiers in Cell and Developmental Biology
Volume9
DOIs
Publication statusPublished - 2021 Sep 6

All Science Journal Classification (ASJC) codes

  • Developmental Biology
  • Cell Biology

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