Video_2_Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression.MP4
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.
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References
- https://doi.org//10.1158/1078-0432.CCR-20-1679
- https://doi.org//10.1016/j.febslet.2015.09.021
- https://doi.org//10.3389/fonc.2021.596798
- https://doi.org//10.1093/glycob/cwl025
- https://doi.org//10.1038/cdd.2012.146
- https://doi.org//10.1073/pnas.1706559114
- https://doi.org//10.1186/s13046-016-0449-1
- https://doi.org//10.3390/biom10050750
- https://doi.org//10.1083/jcb.201905028
- https://doi.org//10.1158/0008-5472.CAN-12-2418
- https://doi.org//10.12688/f1000research.6946.1
- https://doi.org//10.1016/j.jaut.2015.08.020
- https://doi.org//10.2174/1389557519666190304120821
- https://doi.org//10.1038/labinvest.3700420
- https://doi.org//10.1007/s00018-017-2595-9
- https://doi.org//10.7150/jca.51346
- https://doi.org//10.1016/j.cell.2012.11.001
- https://doi.org//10.1242/jcs.222034
- https://doi.org//10.1038/s41421-020-0166-y
- https://doi.org//10.1002/bab.2104
- https://doi.org//10.3748/wjg.v19.i14.2262
- https://doi.org//10.1007/978-3-030-43093-1_2
- https://doi.org//10.1177/002215540205000105
- https://doi.org//10.1038/ng1180
- https://doi.org//10.4049/jimmunol.1303213
- https://doi.org//10.3389/fmolb.2020.586483
- https://doi.org//10.3892/or.2017.5533
- https://doi.org//10.1016/j.semcdb.2018.02.022
- https://doi.org//10.1007/s12072-020-10104-3
- https://doi.org//10.1080/13543776.2021.1903430
- https://doi.org//10.1097/MD.0000000000019622
- https://doi.org//10.1038/s41598-020-70137-4
- https://doi.org//10.3322/caac.21442
- https://doi.org//10.2119/molmed.2009.00119
- https://doi.org//10.1007/s10620-019-05538-1
- https://doi.org//10.1371/journal.pone.0148408
- https://doi.org//10.1073/pnas.0506580102
- https://doi.org//10.1146/annurev-immunol-041015-055402
- https://doi.org//10.1053/j.gastro.2017.01.009
- https://doi.org//10.7150/jca.17648
- https://doi.org//10.1111/j.1440-1746.2012.07130.x
- https://doi.org//10.1186/s12935-018-0607-y
- https://doi.org//10.1136/gutjnl-2014-307671
- https://doi.org//10.3389/fphar.2020.00901
- https://doi.org//10.7554/eLife.11205
- https://doi.org//10.1038/cddis.2015.324
- https://doi.org//10.1016/j.cell.2019.10.003
- https://doi.org//10.1186/s13046-021-01873-2
- https://doi.org//10.1093/abbs/gmw019
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