Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

The critical role of STAT3 in biogenesis of tumor-derived exosomes with potency of inducing cancer cachexia in vitro and in vivo

Abstract

Tumor-derived exosomes are emerging mediators of cancer cachexia. Clarifying the regulation of exosome biogenesis and finding possible targets for cancer cachexia therapy are important and necessary. In the present study, systemic analysis of the roles of STAT3 in controlling exosome biogenesis of murine C26 colon tumor cells and its contribution to the development of cancer cachexia is conducted. The genetic manipulation of STAT3 expression, STAT3 knockout (KO) or overexpression (OE), significantly affected the exosome biogenesis and also the potency of C26 conditioned medium (CM) in inducing muscle atrophy and lipolysis in vitro. The genetic manipulation of STAT3 expression caused change in phosphorylation of PKM2 and glycolysis. PKM2/SNAP23 pathway was involved in regulation of exosome biogenesis by STAT3 genetic manipulation as well as by STAT3 inhibitors in C26 cells. Mice inoculated with STAT3 knockout or overexpression C26 cells exhibited ameliorated or aggravated cancer cachexia symptoms, with a positive correlation with the serum exosome and IL-6 levels. The STAT3/PKM2/SNAP23 pathway was affected in C26 tumor tissues with genetic manipulation of STAT3 expression. The capacity of exosome biogenesis of different human cancer cells also exhibited a positive correlation with the activation of STAT3/PKM2/SNAP23 pathway. The research presented here confirms that STAT3 plays a critical role in regulating biogenesis of tumor-derived exosomes which could contribute to cancer cachexia development.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Changes in STAT3 expression level and activation could influence the biogenesis of exosomes in C26 cells.
Fig. 2: Effects of CM of C26-STAT3-KO or C26-STAT3-OE cells in inducing atrophy of C2C12 myotubes and lipolysis of 3T3-L1 adipocytes.
Fig. 3: The STAT3/PKM2/SNAP23 pathway might be involved in the exosome biogenesis regulation.
Fig. 4: Effects of C26-STAT3-KO or C26-STAT3-OE cells in inducing cancer cachexia in mice.
Fig. 5: Effects of C26-STAT3-KO or C26-STAT3-OE cells in inducing muscle atrophy and fat loss in mice.
Fig. 6: The roles of STAT3 in the regulation of exosome biogenesis in human cancer cells.
Fig. 7: STAT3 activates PKM2 and SNAP23 phosphorylation to regulate the exosome secretion of C26 tumor cells which is involved in the induction of cancer cachexia.

Similar content being viewed by others

References

  1. Baracos VE, Martin L, Korc M, Guttridge DC, Fearon KCH. Cancer-associated cachexia. Nat Rev Dis Prim. 2018;4:17105.

    Article  PubMed  Google Scholar 

  2. Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12:489–95.

    Article  PubMed  Google Scholar 

  3. Prado BL, Qian Y. Anti-cytokines in the treatment of cancer cachexia. Ann Palliat Med. 2019;8:67–79.

    Article  PubMed  Google Scholar 

  4. Gao X, Wang Y, Lu F, Chen X, Yang D, Cao Y, et al. Extracellular vesicles derived from oesophageal cancer containing P4HB promote muscle wasting via regulating PHGDH/Bcl-2/caspase-3 pathway. J Extracell Vesicles. 2021;10:e12060.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Chitti SV, Fonseka P, Mathivanan S. Emerging role of extracellular vesicles in mediating cancer cachexia. Biochem Soc Trans. 2018;46:1129–36.

    Article  CAS  PubMed  Google Scholar 

  6. Marinho R, Alcântara PSM, Ottoch JP, Seelaender M. Role of Exosomal MicroRNAs and myomiRs in the development of cancer cachexia-associated muscle wasting. Front Nutr. 2017;4:69.

    Article  PubMed  Google Scholar 

  7. Hu W, Ru Z, Xiao W, Xiong Z, Wang C, Yuan C, et al. Adipose tissue browning in cancer-associated cachexia can be attenuated by inhibition of exosome generation. Biochem Biophys Res Commun. 2018;506:122–9.

    Article  CAS  PubMed  Google Scholar 

  8. Zhou L, Zhang T, Shao W, Lu R, Wang L, Liu H, et al. Amiloride ameliorates muscle wasting in cancer cachexia through inhibiting tumor-derived exosome release. Skelet Muscle. 2021;11:17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yáñez-Mó M, Siljander PR, Andreu Z, Zavec AB, Borràs FE, Buzas EI, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066.

    Article  PubMed  Google Scholar 

  10. Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002;2:569–79.

    Article  PubMed  Google Scholar 

  11. Simon T, Jackson E, Giamas G. Breaking through the glioblastoma micro-environment via extracellular vesicles. Oncogene. 2020;39:4477–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wendler F, Favicchio R, Simon T, Alifrangis C, Stebbing J, Giamas G. Extracellular vesicles swarm the cancer microenvironment: from tumor-stroma communication to drug intervention. Oncogene. 2017;36:877–84.

    Article  CAS  PubMed  Google Scholar 

  13. D’Souza-Schorey C, Clancy JW. Tumor-derived microvesicles: shedding light on novel microenvironment modulators and prospective cancer biomarkers. Genes Dev. 2012;26:1287–99.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kunou S, Shimada K, Takai M, Sakamoto A, Aoki T, Hikita T, et al. Exosomes secreted from cancer-associated fibroblasts elicit anti-pyrimidine drug resistance through modulation of its transporter in malignant lymphoma. Oncogene. 2021;40:3989–4003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Yang X, Chen Y, Zhou Y, Wu C, Li Q, Wu J, et al. GPC5 suppresses lung cancer progression and metastasis via intracellular CTDSP1/AhR/ARNT signaling axis and extracellular exosome secretion. Oncogene. 2021;40:4307–23.

    Article  CAS  PubMed  Google Scholar 

  16. Miao C, Zhang W, Feng L, Gu X, Shen Q, Lu S, et al. Cancer-derived exosome miRNAs induce skeletal muscle wasting by Bcl-2-mediated apoptosis in colon cancer cachexia. Mol Ther - Nucleic Acids. 2021;24:923–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Harada Y, Nakajima K, Suzuki T, Fukushige T, Kondo K, Seino J, et al. Glycometabolic regulation of the biogenesis of small extracellular vesicles. Cell Rep. 2020;33:108261.

    Article  CAS  PubMed  Google Scholar 

  18. Rice GE, Scholz-Romero K, Sweeney E, Peiris H, Kobayashi M, Duncombe G, et al. The effect of glucose on the release and bioactivity of exosomes from first trimester trophoblast cells. J Clin Endocrinol Metab. 2015;100:E1280–88.

    Article  CAS  PubMed  Google Scholar 

  19. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367:eaau6977.

    Article  PubMed  PubMed Central  Google Scholar 

  20. McAndrews KM, Kalluri R. Mechanisms associated with biogenesis of exosomes in cancer. Mol Cancer. 2019;18:52.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Wei Y, Wang D, Jin F, Bian Z, Li L, Liang H, et al. Pyruvate kinase type M2 promotes tumour cell exosome release via phosphorylating synaptosome-associated protein 23. Nat Commun. 2017;8:14041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Chai EZ, Shanmugam MK, Arfuso F, Dharmarajan A, Wang C, Kumar AP, et al. Targeting transcription factor STAT3 for cancer prevention and therapy. Pharm Ther. 2016;162:86–97.

    Article  CAS  Google Scholar 

  23. Valle-Mendiola A, Soto-Cruz I. Energy metabolism in cancer: the roles of STAT3 and STAT5 in the regulation of metabolism-related genes. Cancers. 2020;12:124.

    Article  PubMed Central  Google Scholar 

  24. Miller A, McLeod L, Alhayyani S, Szczepny A, Watkins DN, Chen W, et al. Blockade of the IL-6 trans-signalling/STAT3 axis suppresses cachexia in Kras-induced lung adenocarcinoma. Oncogene. 2017;36:3059–66.

    Article  CAS  PubMed  Google Scholar 

  25. Zimmers TA, Fishel ML, Bonetto A. STAT3 in the systemic inflammation of cancer cachexia. Semin Cell Dev Biol. 2016;54:28–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Eskiler GG, Bezdegumeli E, Ozman Z, Ozkan AD, Bilir C, Kucukakca BN, et al. IL-6 mediated JAK/STAT3 signaling pathway in cancer patients with cachexia. Bratisl Lek Listy. 2019;66:819–26.

    PubMed  Google Scholar 

  27. Seto DN, Kandarian SC, Jackman RW. A key role for leukemia inhibitory factor in C26 cancer cachexia. J Biol Chem. 2015;290:19976–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Jaśkiewicz A, Domoradzki T, Pająk B. Targeting the JAK2/STAT3 pathway-can we compare it to the two faces of the God Janus? Int J Mol Sci.2020;21:8261.

    Article  PubMed Central  Google Scholar 

  29. Arora G, Gupta A, Guo T, Gandhi A, Laine A, Williams D, et al. JAK inhibitors suppress cancer cachexia-associated anorexia and adipose wasting in mice. JCSM Rapid Commun. 2020;3:115–28.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Chen L, Yang Q, Zhang H, Wan L, Xin B, Cao Y, et al. Cryptotanshinone prevents muscle wasting in CT26-induced cancer cachexia through inhibiting STAT3 signaling pathway. J Ethnopharmacol. 2020;260:113066.

    Article  CAS  PubMed  Google Scholar 

  31. Chen L, Xu W, Yang Q, Zhang H, Wan L, Xin B, et al. Imperatorin alleviates cancer cachexia and prevents muscle wasting via directly inhibiting STAT3. Pharm Res. 2020;158:104871.

    Article  CAS  Google Scholar 

  32. Shouda T, Hiraoka K, Komiya S, Hamada T, Zenmyo M, Iwasaki H, et al. Suppression of IL-6 production and proliferation by blocking STAT3 activation in malignant soft tissue tumor cells. Cancer Lett. 2006;231:176–84.

    Article  CAS  PubMed  Google Scholar 

  33. Shin MK, Sasaki F, Ki DW, Win NN, Morita H, Hayakawa Y. Identification of Ophiocordyceps gracilioides by its anti-tumor effects through targeting the NFκB-STAT3-IL-6 inflammatory pathway. Biol Pharm Bull. 2021;44:686–90.

    Article  CAS  PubMed  Google Scholar 

  34. Rodriguez-Barrueco R, Yu J, Saucedo-Cuevas LP, Olivan M, Llobet-Navas D, Putcha P, et al. Inhibition of the autocrine IL-6-JAK2-STAT3-calprotectin axis as targeted therapy for HR-/HER2+ breast cancers. Genes Dev. 2015;29:1631–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kroon P, Berry PA, Stower MJ, Rodrigues G, Mann VM, Simms M, et al. JAK-STAT blockade inhibits tumor initiation and clonogenic recovery of prostate cancer stem-like cells. Cancer Res. 2013;73:5288–98.

    Article  CAS  PubMed  Google Scholar 

  36. Dorayappan KDP, Wanner R, Wallbillich JJ, Saini U, Zingarelli R, Suarez AA, et al. Hypoxia-induced exosomes contribute to a more aggressive and chemoresistant ovarian cancer phenotype: a novel mechanism linking STAT3/Rab proteins. Oncogene. 2018;37:3806–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ren R, Sun H, Ma C, Liu J, Wang H. Colon cancer cells secrete exosomes to promote self-proliferation by shortening mitosis duration and activation of STAT3 in a hypoxic environment. Cell Biosci. 2019;9:62.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Kosgodage US, Mould R, Henley AB, Nunn AV, Guy GW, Thomas EL, et al. Cannabidiol (CBD) is a novel inhibitor for Exosome and Microvesicle (EMV) release in cancer. Front Pharm. 2018;9:889.

    Article  Google Scholar 

  39. Silva KA, Dong J, Dong Y, Dong Y, Schor N, Tweardy DJ, et al. Inhibition of Stat3 activation suppresses caspase-3 and the ubiquitin-proteasome system, leading to preservation of muscle mass in cancer cachexia. J Biol Chem. 2015;290:11177–87.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Zhang WL, Li N, Shen Q, Fan M, Guo XD, Zhang XW, et al. Establishment of a mouse model of cancer cachexia with spleen deficiency syndrome and the effects of atractylenolide I. Acta Pharm Sin. 2020;41:237–48.

    Article  CAS  Google Scholar 

  41. Fu XQ, Chou JY, Li T, Zhu PL, Li JK, Yin CL, et al. The JAK2/STAT3 pathway is involved in the anti-melanoma effects of atractylenolide I. Exp Dermatol. 2018;27:201–4.

    Article  CAS  PubMed  Google Scholar 

  42. Liu Y, Jia Z, Dong L, Wang R, Qiu G. A randomized pilot study of atractylenolide I on gastric cancer cachexia patients. Evid Based Complement Altern Med. 2008;5:337–44.

    Article  Google Scholar 

  43. Suzuki T, Von Haehling S, Springer J. Promising models for cancer-induced cachexia drug discovery. Expert Opin Drug Disco. 2020;15:627–37.

    Article  CAS  Google Scholar 

  44. Kalra H, Drummen GP, Mathivanan S. Focus on extracellular vesicles: introducing the next small big thing. Int J Mol Sci. 2016;17:170.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Strassmann G, Fong M, Kenney JS, Jacob CO. Evidence for the involvement of interleukin 6 in experimental cancer cachexia. J Clin Invest. 1992;89:1681–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Bonetto A, Aydogdu T, Jin X, Zhang Z, Zhan R, Puzis L, et al. JAK/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia. Am J Physiol Endocrinol Metab. 2012;303:E410–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Fearon KC, Glass DJ, Guttridge DC. Cancer cachexia: mediators, signaling, and metabolic pathways. Cell Metab. 2012;16:153–66.

    Article  CAS  PubMed  Google Scholar 

  48. Sun L, Quan XQ, Yu S. An Epidemiological survey of cachexia in advanced cancer patients and analysis on its diagnostic and treatment status. Nutr Cancer. 2015;67:1056–62.

    Article  PubMed  Google Scholar 

  49. Lu S, Li Y, Shen Q, Zhang W, Gu X, Ma M, et al. Carnosol and its analogues attenuate muscle atrophy and fat lipolysis induced by cancer cachexia. J Cachexia Sarcopenia Muscle. 2021;12:779–95.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Wu Q, Sun S, Li Z, Yang Q, Li B, Zhu S, et al. Tumour-originated exosomal miR-155 triggers cancer-associated cachexia to promote tumour progression. Mol Cancer. 2018;17:155.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Wu Q, Sun S, Li Z, Yang Q, Li B, Zhu S, et al. Breast cancer-released exosomes trigger cancer-associated cachexia to promote tumor progression. Adipocyte. 2019;8:31–45.

    CAS  PubMed  Google Scholar 

  52. Zhang G, Liu Z, Ding H, Zhou Y, Doan HA, Sin KWT, et al. Tumor induces muscle wasting in mice through releasing extracellular Hsp70 and Hsp90. Nat Commun. 2017;8:589.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Kim NH, Sung NJ, Youn HS, Park SA. Gremlin-1 activates Akt/STAT3 signaling, which increases the glycolysis rate in breast cancer cells. Biochem Biophys Res Commun. 2020;533:1378–84.

    Article  CAS  PubMed  Google Scholar 

  54. Bi YH, Han WQ, Li RF, Wang YJ, Du ZS, Wang XJ, et al. Signal transducer and activator of transcription 3 promotes the Warburg effect possibly by inducing pyruvate kinase M2 phosphorylation in liver precancerous lesions. World J Gastroenterol. 2019;25:1936–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Zhao W, Guo W, Zhou Q, Ma SN, Wang R, Qiu Y, et al. In vitro antimetastatic effect of phosphatidylinositol 3-kinase inhibitor ZSTK474 on prostate cancer PC3 cells. Int J Mol Sci. 2013;14:13577–91.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Marrocco I, Altieri F, Rubini E, Paglia G, Chichiarelli S, Giamogante F, et al. Shmt2: a Stat3 signaling new player in prostate cancer energy metabolism. Cells. 2019;8:1048.

    Article  PubMed Central  Google Scholar 

  57. Demaria M, Poli V. PKM2, STAT3 and HIF-1α: the Warburg’s vicious circle. Jakstat. 2012;1:194–6.

    PubMed  PubMed Central  Google Scholar 

  58. Vallee A, Guillevin R, Vallee JN. Vasculogenesis and angiogenesis initiation under normoxic conditions through Wnt/beta-catenin pathway in gliomas. Rev Neurosci. 2018;29:71–91.

    Article  CAS  PubMed  Google Scholar 

  59. Yang M, Wang L, Wang X, Wang X, Yang Z, Li J. IL-6 promotes FSH-induced VEGF expression through JAK/STAT3 signaling pathway in bovine granulosa cells. Cell Physiol Biochem. 2017;44:293–302.

    Article  CAS  PubMed  Google Scholar 

  60. Pawlus MR, Wang L, Murakami A, Dai G, Hu CJ. STAT3 or USF2 contributes to HIF target gene specificity. PLoS One. 2013;8:e72358.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Altenberg B, Greulich KO. Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes. Genomics. 2004;84:1014–20.

    Article  CAS  PubMed  Google Scholar 

  62. Chaneton B, Gottlieb E. Rocking cell metabolism: revised functions of the key glycolytic regulator PKM2 in cancer. Trends Biochem Sci. 2012;37:309–16.

    Article  CAS  PubMed  Google Scholar 

  63. Puckett DL, Alquraishi M, Chowanadisai W, Bettaieb A. The role of PKM2 in metabolic reprogramming: insights into the regulatory roles of non-coding RNAs. Int J Mol Sci.2021;22:1171.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Vaupel P, Multhoff G. Revisiting the Warburg effect: historical dogma versus current understanding. J Physiol. 2021;599:1745–57.

    Article  CAS  PubMed  Google Scholar 

  65. Zahra K, Dey T, Ashish, Mishra SP, Pandey U. Pyruvate Kinase M2 and cancer: the role of PKM2 in promoting tumorigenesis. Front Oncol. 2020;10:159.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Palsson-McDermott EM, O’Neill LA. The Warburg effect then and now: from cancer to inflammatory diseases. Bioessays. 2013;35:965–73.

    Article  CAS  PubMed  Google Scholar 

  67. Yoon YJ, Kim YH, Jin Y, Chi SW, Moon JH, Han DC, et al. 2’-hydroxycinnamaldehyde inhibits cancer cell proliferation and tumor growth by targeting the pyruvate kinase M2. Cancer Lett. 2018;434:42–55.

    Article  CAS  PubMed  Google Scholar 

  68. Li Y, Wang Y, Liu Z, Guo X, Miao Z, Ma S. Atractylenolide I induces apoptosis and suppresses glycolysis by blocking the JAK2/STAT3 signaling pathway in colorectal cancer cells. Front Pharm. 2020;11:273.

    Article  CAS  Google Scholar 

  69. Zhang Q, Liu Q, Zheng S, Liu T, Yang L, Han X, et al. Shikonin inhibits tumor growth of ESCC by suppressing PKM2 mediated aerobic glycolysis and STAT3 phosphorylation. J Cancer. 2021;12:4830–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Gao S, Chen M, Wei W, Zhang X, Zhang M, Yao Y, et al. Crosstalk of mTOR/PKM2 and STAT3/c-Myc signaling pathways regulate the energy metabolism and acidic microenvironment of gastric cancer. J Cell Biochem. 2018;120:1193–1202.

    Article  Google Scholar 

  71. Gao X, Wang H, Yang JJ, Liu X, Liu ZR. Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase. Mol Cell. 2012;45:598–609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Shirai T, Nazarewicz RR, Wallis BB, Yanes RE, Watanabe R, Hilhorst M, et al. The glycolytic enzyme PKM2 bridges metabolic and inflammatory dysfunction in coronary artery disease. J Exp Med. 2016;213:337–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Bian Z, Zhang J, Li M, Feng Y, Wang X, Zhang J, et al. LncRNA-FEZF1-AS1 Promotes tumor proliferation and metastasis in colorectal cancer by regulating PKM2 signaling. Clin Cancer Res. 2018;24:4808–19.

    Article  CAS  PubMed  Google Scholar 

  74. Damasceno LEA, Prado DS, Veras FP, Fonseca MM, Toller-Kawahisa JE, Rosa MH, et al. PKM2 promotes Th17 cell differentiation and autoimmune inflammation by fine-tuning STAT3 activation. J Exp Med. 2020;217:e20190613.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Ou B, Sun H, Zhao J, Xu Z, Liu Y, Feng H, et al. Polo-like kinase 3 inhibits glucose metabolism in colorectal cancer by targeting HSP90/STAT3/HK2 signaling. J Exp Clin Cancer Res. 2019;38:426.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Li M, Jin R, Wang W, Zhang T, Sang J, Li N, et al. STAT3 regulates glycolysis via targeting hexokinase 2 in hepatocellular carcinoma cells. Oncotarget. 2017;8:24777–84.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Galli T, Zahraoui A, Vaidyanathan VV, Raposo G, Tian JM, Karin M, et al. A novel tetanus neurotoxin-insensitive vesicle-associated membrane protein in SNARE complexes of the apical plasma membrane of epithelial cells. Mol Biol Cell. 1998;9:1437–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Puri N, Roche PA. Ternary SNARE complexes are enriched in lipid rafts during mast cell exocytosis. Traffic. 2006;7:1482–94.

    Article  CAS  PubMed  Google Scholar 

  79. Redell MS, Ruiz MJ, Alonzo TA, Gerbing RB, Tweardy DJ. Stat3 signaling in acute myeloid leukemia: ligand-dependent and -independent activation and induction of apoptosis by a novel small-molecule Stat3 inhibitor. Blood. 2011;117:5701–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Zhu B, Zhang QL, Hua JW, Cheng WL, Qin LP. The traditional uses, phytochemistry, and pharmacology of Atractylodes macrocephala Koidz.: a review. J Ethnopharmacol. 2018;226:143–67.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by National Nature Science Foundation of China (No. 81872496 and 81873056), and the Science and Technology Commission of Shanghai Municipality (20S11902200 and 16DZ2280100).

Author information

Authors and Affiliations

Authors

Contributions

MF performed the experiments, analyzed the data, and drafted the manuscript. WS, XG, SL, and QS were involved in performing the experiments. XL and XZ supervised the project, designed the study, and revised the manuscript. All authors reviewed and approved the final manuscript.

Corresponding authors

Correspondence to Xuan Liu or Xiongwen Zhang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fan, M., Sun, W., Gu, X. et al. The critical role of STAT3 in biogenesis of tumor-derived exosomes with potency of inducing cancer cachexia in vitro and in vivo. Oncogene 41, 1050–1062 (2022). https://doi.org/10.1038/s41388-021-02151-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41388-021-02151-3

This article is cited by

Search

Quick links