Blockade of DDR1/PYK2/ERK signaling suggesting SH2 superbinder as a novel autophagy inhibitor for pancreatic cancer.
Blockade of DDR1/PYK2/ERK signaling suggesting SH2 superbinder as a novel autophagy inhibitor for pancreatic cancer.
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DOI：
10.1038/s41419-023-06344-4
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发表时间：
2023-12-09
影响因子：
9
通讯作者：
Liu, An-Dong
中科院分区：
文献类型：
--
作者：
Xu, Hui;Tan, Ming;Hou, Guo-Qing;Sang, Ya-Zhou;Lin, Li;Gan, Xiao-Cai;Cao, Xuan;Liu, An-Dong
胰腺癌致死率高，其中90%为胰腺导管腺癌（PDAC），5年生存率不足12%，缺乏有效治疗方案，诊断较晚。此外，肿瘤显示出对细胞毒性化疗的强烈抗性。由于自噬在PDAC中升高，靶向自噬途径被认为是癌症治疗的有希望的策略。免疫荧光和透射电子显微镜用于评估自噬通量。无标记的定量磷酸蛋白质组学被用来找出严重改变的酪氨酸磷酸化的蛋白质。用荷瘤小鼠验证SH 2 TrM-（Arg）9抑制肿瘤细胞生长。SH 2 TrM-（Arg）9通过阻断DDR 1/PYK 2/ERK信号通路抑制胶原诱导的自噬。SH 2 TrM-（Arg）9可提高PANC-1/GEM细胞对吉西他滨（GEM）的敏感性。SH 2 TrM-（Arg）9对自噬的抑制可能与胰腺癌异种移植物中的化疗和破坏的肿瘤抑制协同作用。SH 2 TrM-（Arg）9可进入PDAC细胞，通过抑制DDR 1/PYK 2/ERK信号通路阻断自噬，有望成为PDAC靶向治疗的新策略。
Pancreatic cancer is highly lethal, of which 90% is pancreatic ductal adenocarcinoma (PDAC), with a 5-year survival rate of less than 12%, lacking effective treatment options and late diagnosis. Furthermore, the tumors show an intense resistance to cytotoxic chemotherapies. As autophagy is elevated in PDAC, targeting the autophagic pathway is regarded as a promising strategy for cancer treatment. Immunofluorescence and transmission electron microscopy were utilized to assess the autophagic flux. Label-free quantitative phosphoproteomics was used to figure out critically altered tyrosine phosphorylation of the proteins. Tumor-bearing mice were used to validate that SH2 TrM-(Arg)9 restrained the growth of tumor cells. SH2 TrM-(Arg)9 inhibited collagen-induced autophagy via blocking the DDR1/PYK2/ERK signaling cascades. SH2 TrM-(Arg)9 improved the sensitivity of PANC-1/GEM cells to gemcitabine (GEM). Inhibition of autophagy by SH2 TrM-(Arg)9 may synergized with chemotherapy and robusted tumor suppression in pancreatic cancer xenografts. SH2 TrM-(Arg)9 could enter into PDAC cells and blockade autophagy through inhibiting DDR1/PYK2/ERK signaling and may be a new treatment strategy for targeted therapy of PDAC.
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影响因子：
16.6
作者：
Huang H;Ouyang Q;Zhu M;Yu H;Mei K;Liu R
通讯作者：
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DOI：
10.1186/s13046-015-0202-1
发表时间：
2015-08-22
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
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影响因子：
37.3
作者：
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Lovly CM
影响因子：
2.9
作者：
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通讯作者：
Guan, Zhong
影响因子：
3.5
作者：
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Moussa, Charbel