Early Infiltration of Innate Immune Cells to the Liver Depletes HNF4α and Promotes Extrahepatic Carcinogenesis.
Early Infiltration of Innate Immune Cells to the Liver Depletes HNF4α and Promotes Extrahepatic Carcinogenesis.
复制标题
先天免疫细胞早期浸润肝脏消耗HNF4α并促进肝外癌的发生
DOI：
10.1158/2159-8290.cd-22-1062
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发表时间：
2023-07-07
期刊：
影响因子：
28.2
通讯作者：
Erez, Ayelet
中科院分区：
文献类型：
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作者：
Goldman, Omer;Adler, Lital N.;Hajaj, Emma;Croese, Tommaso;Darzi, Naama;Galai, Sivan;Tishler, Hila;Ariav, Yarden;Lavie, Dor;Fellus-Alyagor, Liat;Oren, Roni;Kuznetsov, Yuri;David, Eyal;Jaschek, Rami;Stossel, Chani;Singer, Oded;Malitsky, Sergey;Barak, Renana;Seger, Rony;Erez, Neta;Amit, Ido;Tanay, Amos;Saada, Ann;Golan, Talia;Rubinek, Tamar;Sang Lee, Joo;Ben-Shachar, Shay;Wolf, Ido;Erez, Ayelet
Metabolic rewiring of liver metabolism by extrahepatic tumors via innate immune cells occurs at the early disease stage, promoting tumor progression and cancer-related systemic manifestations, such as weight loss. Multiple studies have identified metabolic changes within the tumor and its microenvironment during carcinogenesis. Yet, the mechanisms by which tumors affect the host metabolism are unclear. We find that systemic inflammation induced by cancer leads to liver infiltration of myeloid cells at early extrahepatic carcinogenesis. The infiltrating immune cells via IL6–pSTAT3 immune–hepatocyte cross-talk cause the depletion of a master metabolic regulator, HNF4α, consequently leading to systemic metabolic changes that promote breast and pancreatic cancer proliferation and a worse outcome. Preserving HNF4α levels maintains liver metabolism and restricts carcinogenesis. Standard liver biochemical tests can identify early metabolic changes and predict patients’ outcomes and weight loss. Thus, the tumor induces early metabolic changes in its macroenvironment with diagnostic and potentially therapeutic implications for the host. Cancer growth requires a permanent nutrient supply starting from early disease stages. We find that the tumor extends its effect to the host's liver to obtain nutrients and rewires the systemic and tissue-specific metabolism early during carcinogenesis. Preserving liver metabolism restricts tumor growth and improves cancer outcomes. This article is highlighted in the In This Issue feature, p. 1501
DOI：
10.3390/life11080755
发表时间：
2021-07-27
期刊：
Life (Basel, Switzerland)
影响因子：
--
作者：
Gaál Z;Szűcs Z;Kántor I;Luczay A;Tóth-Heyn P;Benn O;Felszeghy E;Karádi Z;Madar L;Balogh I
通讯作者：
Balogh I