Type IV collagen α5 chain promotes luminal breast cancer progression through c-Myc-driven glycolysis.
Type IV collagen α5 chain promotes luminal breast cancer progression through c-Myc-driven glycolysis.
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IV 型胶原蛋白 α5 链通过 c-Myc 驱动的糖酵解促进管腔乳腺癌进展
DOI：
10.1093/jmcb/mjac068
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发表时间：
2023-03-29
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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作者：
癌细胞代谢重编程是癌症的标志之一。癌细胞优先利用有氧糖酵解，这一过程受激活的癌基因和肿瘤微环境调控。肿瘤微环境中的细胞外基质（ECM），包括基底膜（BMs），处于动态重塑状态。然而，ECM是否以及如何调节肿瘤糖酵解在很大程度上仍不明确。我们发现，IV型胶原蛋白是维持组织完整性和正常功能所必需的BMs成分，在乳腺癌亚型中存在差异表达，其中α5链（α5(IV)）在管腔型乳腺癌中优先表达，并受雌激素受体-α调控。α5(IV)对于管腔型乳腺癌的发展不可或缺。敲除α5(IV)会显著降低管腔型乳腺癌细胞的生长，并阻碍管腔型乳腺癌的发展。α5(IV)敲除的管腔型乳腺癌细胞生长受损和肿瘤发展能力下降，归因于管腔型乳腺癌细胞中葡萄糖转运蛋白和糖酵解酶的表达降低以及糖酵解受损。在α5(IV)敲除的管腔型乳腺癌细胞中，非整合素胶原蛋白受体盘状结构域受体-1（DDR1）的表达和p38丝裂原活化蛋白激酶的激活减弱，导致癌基因c-Myc的表达和磷酸化降低。持续激活的DDR1或c-Myc的异位表达可恢复葡萄糖转运蛋白和糖酵解酶的表达，进而恢复管腔型乳腺癌的有氧糖酵解、细胞增殖和肿瘤生长。因此，IV型胶原蛋白α5链是一种管腔型乳腺癌特异性的微环境调节因子，可调节癌细胞代谢。
Cancer cell metabolism reprogramming is one of the hallmarks of cancer. Cancer cells preferentially utilize aerobic glycolysis, which is regulated by activated oncogenes and the tumor microenvironment. Extracellular matrix (ECM) in the tumor microenvironment, including the basement membranes (BMs), is dynamically remodeled. However, whether and how ECM regulates tumor glycolysis is largely unknown. We show that type IV collagens, components of BMs essential for the tissue integrity and proper function, are differentially expressed in breast cancer subtypes that α5 chain (α5(IV)) is preferentially expressed in the luminal-type breast cancer and is regulated by estrogen receptor-α. α5(IV) is indispensable for luminal breast cancer development. Ablation of α5(IV) significantly reduces the growth of luminal-type breast cancer cells and impedes the development of luminal-type breast cancer. Impaired cell growth and tumor development capability of α5(IV)-ablated luminal breast cancer cells is attributed to the reduced expression of glucose transporter and glycolytic enzymes and impaired glycolysis in luminal breast cancer cells. Non-integrin collagen receptor discoidin domain receptor-1 (DDR1) expression and p38 mitogen-activated protein kinase activation are attenuated in α5(IV)-ablated luminal breast cancer cells, resulting in reduced c-Myc oncogene expression and phosphorylation. Ectopic expression of constitutively active DDR1 or c-Myc restores the expression of glucose transporter and glycolytic enzymes, and thereafter restores aerobic glycolysis, cell proliferation, and tumor growth of luminal breast cancer. Thus, type IV collagen α5 chain is a luminal-type breast cancer-specific microenvironmental regulator modulating cancer cell metabolism.
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DOI：
10.1001/jama.2011.593
发表时间：
2011-05-11
期刊：
JAMA
影响因子：
--
作者：
Hatzis C;Pusztai L;Valero V;Booser DJ;Esserman L;Lluch A;Vidaurre T;Holmes F;Souchon E;Wang H;Martin M;Cotrina J;Gomez H;Hubbard R;Chacón JI;Ferrer-Lozano J;Dyer R;Buxton M;Gong Y;Wu Y;Ibrahim N;Andreopoulou E;Ueno NT;Hunt K;Yang W;Nazario A;DeMichele A;O'Shaughnessy J;Hortobagyi GN;Symmans WF
通讯作者：
Symmans WF
影响因子：
16.6
作者：
Li Z;Ivanov AA;Su R;Gonzalez-Pecchi V;Qi Q;Liu S;Webber P;McMillan E;Rusnak L;Pham C;Chen X;Mo X;Revennaugh B;Zhou W;Marcus A;Harati S;Chen X;Johns MA;White MA;Moreno C;Cooper LA;Du Y;Khuri FR;Fu H
通讯作者：
Fu H
DOI：
10.1002/hep.28918
发表时间：
2017-03
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Massey VL;Dolin CE;Poole LG;Hudson SV;Siow DL;Brock GN;Merchant ML;Wilkey DW;Arteel GE
通讯作者：
Arteel GE
影响因子：
4.6
作者：
Pöschl, E;Schlötzer-Schrehardt, U;Mayer, U
通讯作者：
Mayer, U
影响因子：
6.9
作者：
Bergmeier, Vera;Etich, Julia;Brachvogel, Bent
通讯作者：
Brachvogel, Bent