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EcTI impairs survival and proliferation pathways in triple-negative breast cancer by modulating cell-glycosaminoglycans and inflammatory cytokines.
Cancer Letters ( IF 9.1 ) Pub Date : 2020-08-22 , DOI: 10.1016/j.canlet.2020.08.017
Yara A Lobo 1 , Camila Bonazza 2 , Fabrício P Batista 1 , Rodrigo A Castro 2 , Camila R Bonturi 1 , Bruno R Salu 1 , Rita de Cassia Sinigaglia 3 , Leny Toma 1 , Carolina M Vicente 1 , Giselle Pidde 4 , Denise V Tambourgi 4 , Miryam P Alvarez-Flores 5 , Ana M Chudzinski-Tavassi 5 , Maria Luiza V Oliva 1
Affiliation  

Breast cancer is the most common malignant tumor among women worldwide, and triple-negative breast cancer is the most aggressive type of breast cancer, which does not respond to hormonal therapies. The protease inhibitor, EcTI, extracted from seeds of Enterolobium contortisiliquum, acts on the main signaling pathways of the MDA-MB-231 triple-negative breast cancer cells. This inhibitor, when bound to collagen I of the extracellular matrix, triggers a series of pathways capable of decreasing the viability, adhesion, migration, and invasion of these cells. This inhibitor can interfere in the cell cycle process through the main signaling pathways such as the adhesion, Integrin/FAK/SRC, Akt, ERK, and the cell death pathway BAX and BCL-2. It also acts by reducing the main inflammatory cytokines such as TGF-α, IL-6, IL-8, and MCP-1, besides NFκB, a transcription factor, responsible for the aggressive and metastatic characteristics of this type of tumor. Thus, the inhibitor was able to reduce the main processes of carcinogenesis of this type of cancer.



中文翻译:

EcTI通过调节细胞糖胺聚糖和炎性细胞因子来损害三阴性乳腺癌的生存和增殖途径。

乳腺癌是全世界女性中最常见的恶性肿瘤,三阴性乳腺癌是最激进的乳腺癌,对激素疗法无反应。从肠球菌种子中提取蛋白酶抑制剂EcTI,作用于MDA-MB-231三阴性乳腺癌细胞的主要信号通路。当与细胞外基质的胶原蛋白I结合时,该抑制剂会触发一系列降低这些细胞活力,粘附,迁移和侵袭的途径。该抑制剂可通过主要的信号传导途径(例如粘附,整合素/ FAK / SRC,Akt,ERK和细胞死亡途径BAX和BCL-2)干扰细胞周期过程。它也通过减少主要的炎性细胞因子(例如TGF-α,IL-6,IL-8和MCP-1)来发挥作用,此外还有转录因子NFκB,它负责这种类型肿瘤的侵袭性和转移性。因此,该抑制剂能够减少这类癌症的主要癌变过程。

更新日期:2020-08-22
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