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

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

doi:10.3389/fcell.2021.741820

Cited by 18 publications

(17 citation statements)

References 50 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Focusing on cell biology of galectins, our findings suggest that galectins can be a target of O -GlcNAc-mediated regulation at both gene and protein levels including the secretion of these molecules from cells. Molecular mechanisms of unconventional secretion of galectins, which are synthesized in cytosol, are complex and include possibilities of direct translocation, exosomal and microvesicular trafficking including autophagosomal secretion among others [ 14 , 15 , 49 , 50 ]. As such, many galectins (galectin-1, galectin-3, galectin-4, galectin-7, and galectin-10) are detectable in human plasma by mass spectrometry [ 20 ] and claimed to have diagnostic value for cancer and cardiovascular diseases [ 51 , 52 ] while others like galectin-12 may accumulate in cytoplasm by binding with lipid droplets [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

O-GlcNAc-Mediated Regulation of Galectin Expression and Secretion in Human Promyelocytic HL-60 Cells Undergoing Neutrophilic Differentiation

2022

View full text Add to dashboard Cite

In this study, we have tested the hypothesis that the expression and secretion of galectins are driven through mechanisms globally impacted by homeostatic regulation involving the post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc). We showed that neutrophilic differentiation of HL-60 cells induced by all-trans retinoic acid (ATRA) and 6-diazo-5-oxo-L-norleucine (DON) was associated with a significant drop of cellular O-GlcNAc levels in serum-contained and serum-free cell culture media. Galectin gene and protein expression profiles in HL-60 cells were specifically modified by ATRA and by inhibitors of O-GlcNAc cycle enzymes, however overall trends for each drug were similar between cells growing in the presence or absence of serum except for LGALS9 and LGALS12. The secretion of four galectins (-1, -3, -9, and -10) by HL-60 cells in a serum-free medium was stimulated by O-GlcNAc-reducing ATRA and DON while O-GlcNAc-elevating thiamet G (O-GlcNAcase inhibitor) failed to change the basal levels of extracellular galectins. Taken together, these results demonstrate that O-GlcNAc homeostasis is essential not only for regulation of galectin expression in cells but also for the secretion of multiple members of this protein family, which can be an important novel aspect of unconventional secretion mechanisms.

show abstract

Section: Discussionmentioning

confidence: 99%

O-GlcNAc-Mediated Regulation of Galectin Expression and Secretion in Human Promyelocytic HL-60 Cells Undergoing Neutrophilic Differentiation

2022

View full text Add to dashboard Cite

show abstract

“…This autophagy-regulated galecin-1 secretion promotes tumor growth in mice and correlates to poor prognosis of hepatocellular carcinoma patients. The findings demonstrate the contribution of galectin-1 released by secretory autophagy in TAMs and its role in liver cancer progression [225] (Right, Fig. 6).…”

Section: Galectin-1mentioning

confidence: 70%

Recent advances in conventional and unconventional vesicular secretion pathways in the tumor microenvironment

et al. 2022

Self Cite

View full text Add to dashboard Cite

All cells in the changing tumor microenvironment (TME) need a class of checkpoints to regulate the balance among exocytosis, endocytosis, recycling and degradation. The vesicular trafficking and secretion pathways regulated by the small Rab GTPases and their effectors convey cell growth and migration signals and function as meditators of intercellular communication and molecular transfer. Recent advances suggest that Rab proteins govern conventional and unconventional vesicular secretion pathways by trafficking widely diverse cargoes and substrates in remodeling TME. The mechanisms underlying the regulation of conventional and unconventional vesicular secretion pathways, their action modes and impacts on the cancer and stromal cells have been the focus of much attention for the past two decades. In this review, we discuss the current understanding of vesicular secretion pathways in TME. We begin with an overview of the structure, regulation, substrate recognition and subcellular localization of vesicular secretion pathways. We then systematically discuss how the three fundamental vesicular secretion processes respond to extracellular cues in TME. These processes are the conventional protein secretion via the endoplasmic reticulum-Golgi apparatus route and two types of unconventional protein secretion via extracellular vesicles and secretory autophagy. The latest advances and future directions in vesicular secretion-involved interplays between tumor cells, stromal cell and host immunity are also described.

show abstract

“…58,88 The same color indicates the same process. 89,90 membrane to secrete proteins. 93 Within the microenvironment, both the cancer cells themselves and stromal supporting cells rely on autophagy-dependent secretion for progression of the disease as well as therapy resistance.…”

Section: Polarization Of Tams and Autophagymentioning

confidence: 99%

The regulatory role of autophagy between TAMs and tumor cells

Hu,

Fan,

et al. 2024

Cell Biochemistry & Function

View full text Add to dashboard Cite

Cancer has become a global public health problem and its harmful effects have received widespread attention. Conventional treatments such as surgical resection, radiotherapy and other techniques are applicable to clinical practice, but new drugs are constantly being developed and other therapeutic approaches, such as immunotherapy are being applied. In addition to studying the effects on individual tumor cells, it is important to explore the role of tumor microenvironment on tumor cell development since tumor cells do not exist alone but in the tumor microenvironment. In the tumor microenvironment, tumor cells are interconnected with other stromal cells and influence each other, among which tumor‐associated macrophages (TAMs) are the most numerous immune cells. At the same time, it was found that cancer cells have different levels of autophagy from normal cells. In cancer therapy, the occurrence of autophagy plays an important role in promoting tumor cell death or inhibiting tumor cell death, and is closely related to the environment. Therefore, elucidating the regulatory role of autophagy between TAMs and tumor cells may be an important breakthrough, providing new perspectives for further research on antitumor immune mechanisms and improving the efficacy of cancer immunotherapy.

show abstract

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

Cited by 18 publications

References 50 publications

O-GlcNAc-Mediated Regulation of Galectin Expression and Secretion in Human Promyelocytic HL-60 Cells Undergoing Neutrophilic Differentiation

O-GlcNAc-Mediated Regulation of Galectin Expression and Secretion in Human Promyelocytic HL-60 Cells Undergoing Neutrophilic Differentiation

Recent advances in conventional and unconventional vesicular secretion pathways in the tumor microenvironment

The regulatory role of autophagy between TAMs and tumor cells

Contact Info

Product

Resources

About