Abstract
Dietary effects on tumor biology can be exploited to unravel cancer vulnerabilities. Here, we present surprising evidence for anti-proliferative action of high-calorie-diet (HCD) feeding on KRAS-driven lung tumors. Tumors of mice that commenced HCD feeding before tumor onset displayed defective unfolded protein response (UPR) and unresolved endoplasmic reticulum (ER) stress. Unresolved ER stress and reduced proliferation are reversed by chemical chaperone treatment. Whole-genome transcriptional analyses revealed FKBP10 as one of the most downregulated chaperones in tumors of the HCD-pre-tumor-onset group. FKBP10 downregulation dampens tumor growth in vitro and in vivo. Providing translational value to these results, we report that FKBP10 is expressed in human KRAS-positive and -negative lung cancers, but not in healthy parenchyma. Collectively, our data shed light on an unexpected anti-tumor action of HCD imposed before tumor onset and identify FKBP10 as a putative therapeutic target to selectively hinder lung cancer.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 117-125 |
| Number of pages | 9 |
| Journal | Cell Metabolism |
| Volume | 21 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 6 2015 |
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ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
- Physiology
Cite this
Diet-induced unresolved ER stress hinders KRAS-driven lung tumorigenesis. / Ramadori, Giorgio; Konstantinidou, Georgia; Venkateswaran, Niranjan; Biscotti, Tommasina; Morlock, Lorraine; Galié, Mirco; Williams, Noelle S.; Luchetti, Michele; Santinelli, Alfredo; Scaglioni, Pier Paolo; Coppari, Roberto.
In: Cell Metabolism, Vol. 21, No. 1, 06.01.2015, p. 117-125.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Diet-induced unresolved ER stress hinders KRAS-driven lung tumorigenesis
AU - Ramadori, Giorgio
AU - Konstantinidou, Georgia
AU - Venkateswaran, Niranjan
AU - Biscotti, Tommasina
AU - Morlock, Lorraine
AU - Galié, Mirco
AU - Williams, Noelle S.
AU - Luchetti, Michele
AU - Santinelli, Alfredo
AU - Scaglioni, Pier Paolo
AU - Coppari, Roberto
PY - 2015/1/6
Y1 - 2015/1/6
N2 - Dietary effects on tumor biology can be exploited to unravel cancer vulnerabilities. Here, we present surprising evidence for anti-proliferative action of high-calorie-diet (HCD) feeding on KRAS-driven lung tumors. Tumors of mice that commenced HCD feeding before tumor onset displayed defective unfolded protein response (UPR) and unresolved endoplasmic reticulum (ER) stress. Unresolved ER stress and reduced proliferation are reversed by chemical chaperone treatment. Whole-genome transcriptional analyses revealed FKBP10 as one of the most downregulated chaperones in tumors of the HCD-pre-tumor-onset group. FKBP10 downregulation dampens tumor growth in vitro and in vivo. Providing translational value to these results, we report that FKBP10 is expressed in human KRAS-positive and -negative lung cancers, but not in healthy parenchyma. Collectively, our data shed light on an unexpected anti-tumor action of HCD imposed before tumor onset and identify FKBP10 as a putative therapeutic target to selectively hinder lung cancer.
AB - Dietary effects on tumor biology can be exploited to unravel cancer vulnerabilities. Here, we present surprising evidence for anti-proliferative action of high-calorie-diet (HCD) feeding on KRAS-driven lung tumors. Tumors of mice that commenced HCD feeding before tumor onset displayed defective unfolded protein response (UPR) and unresolved endoplasmic reticulum (ER) stress. Unresolved ER stress and reduced proliferation are reversed by chemical chaperone treatment. Whole-genome transcriptional analyses revealed FKBP10 as one of the most downregulated chaperones in tumors of the HCD-pre-tumor-onset group. FKBP10 downregulation dampens tumor growth in vitro and in vivo. Providing translational value to these results, we report that FKBP10 is expressed in human KRAS-positive and -negative lung cancers, but not in healthy parenchyma. Collectively, our data shed light on an unexpected anti-tumor action of HCD imposed before tumor onset and identify FKBP10 as a putative therapeutic target to selectively hinder lung cancer.
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U2 - 10.1016/j.cmet.2014.11.020
DO - 10.1016/j.cmet.2014.11.020
M3 - Article
C2 - 25533479
AN - SCOPUS:84920656075
VL - 21
SP - 117
EP - 125
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 1
ER -