Glyoxalase 1 and protein kinase Cλ as potential therapeutic targets for late-stage breast cancer.
Glyoxalase 1 and protein kinase Cλ as potential therapeutic targets for late-stage breast cancer.
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DOI：
10.3892/ol.2021.12808
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发表时间：
2021-07
期刊：
影响因子：
2.9
通讯作者：
Akimoto K
中科院分区：
文献类型：
--
作者：
Motomura H;Ozaki A;Tamori S;Onaga C;Nozaki Y;Waki Y;Takasawa R;Yoshizawa K;Mano Y;Sato T;Sasaki K;Ishiguro H;Miyagi Y;Nagashima Y;Yamamoto K;Sato K;Hanawa T;Tanuma SI;Ohno S;Akimoto K
癌细胞上调糖酵解酶的表达水平，以达到糖酵解所需的增加。其中一种上调的糖酵解酶是glyoxalase 1 (GLO 1)，它催化有毒的甲基乙二醛转化为无毒的s - d -乳酸谷胱甘肽。蛋白激酶Cλ (PKCλ)在各种类型的癌症中也上调，并参与癌症的进展。在本研究中，研究了糖酵解增强与PKCλ在乳腺癌中的关系。在人乳腺癌中，GLO - 1的高表达与PKCλ蛋白（P<0.01）和mRNA水平的高表达相关（P<0.01）。此外，Wilcoxon和Cox回归模型分析显示，GLO - 1和PKCλ高表达的III-IV期肿瘤患者的总生存期比表达这些基因水平较低的患者差[P=0.040 （Gehan-Breslow广义Wilcoxon检验）和P=0.031（风险比为2.36,95%置信区间为1.08-5.16）]。用TLSC702 （GLO 1抑制剂）和/或金硫硫酸盐（PKCλ抑制剂）治疗MDA-MB-157和MDA-MB-468人基底样乳腺癌细胞可降低细胞活力和肿瘤球的形成。这些结果表明GLO 1和PKCλ共同参与了乳腺癌的进展，并导致了乳腺癌的不良预后。综上所述，GLO 1和PKCλ可能是治疗晚期人类乳腺癌的有效靶点。
Cancer cells upregulate the expression levels of glycolytic enzymes in order to reach the increased glycolysis required. One such upregulated glycolytic enzyme is glyoxalase 1 (GLO 1), which catalyzes the conversion of toxic methylglyoxal to nontoxic S-D-lactoylglutathione. Protein kinase Cλ (PKCλ) is also upregulated in various types of cancer and is involved in cancer progression. In the present study, the association between enhanced glycolysis and PKCλ in breast cancer was investigated. In human breast cancer, high GLO 1 expression was associated with high PKCλ expression at the protein (P<0.01) and mRNA levels (P<0.01). Furthermore, Wilcoxon and Cox regression model analysis revealed that patients with stage III–IV tumors with high GLO 1 and PKCλ expression had poor overall survival compared with patients expressing lower levels of these genes [P=0.040 (Gehan-Breslow generalized Wilcoxon test) and P=0.031 (hazard ratio, 2.36; 95% confidence interval, 1.08–5.16), respectively]. Treatment of MDA-MB-157 and MDA-MB-468 human basal-like breast cancer cells with TLSC702 (a GLO 1 inhibitor) and/or aurothiomalate (a PKCλ inhibitor) reduced both cell viability and tumor-sphere formation. These results suggested that GLO 1 and PKCλ were cooperatively involved in cancer progression and contributed to a poor prognosis in breast cancer. In conclusion, GLO 1 and PKCλ serve as potentially effective therapeutic targets for treatment of late-stage human breast cancer.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
12.3
作者：
Herschkowitz JI;Simin K;Weigman VJ;Mikaelian I;Usary J;Hu Z;Rasmussen KE;Jones LP;Assefnia S;Chandrasekharan S;Backlund MG;Yin Y;Khramtsov AI;Bastein R;Quackenbush J;Glazer RI;Brown PH;Green JE;Kopelovich L;Furth PA;Palazzo JP;Olopade OI;Bernard PS;Churchill GA;Van Dyke T;Perou CM
通讯作者：
Perou CM
影响因子：
3.7
作者：
Cheng WL;Tsai MM;Tsai CY;Huang YH;Chen CY;Chi HC;Tseng YH;Chao IW;Lin WC;Wu SM;Liang Y;Liao CJ;Lin YH;Chung IH;Chen WJ;Lin PY;Wang CS;Lin KH
通讯作者：
Lin KH
影响因子：
2.8
作者：
Baunacke, Martin;Horn, Lars-Christian;Birkenmeier, Gerd
通讯作者：
Birkenmeier, Gerd
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel