GAIP interacting protein C-terminus regulates autophagy and exosome biogenesis of pancreatic cancer through metabolic pathways.
GAIP interacting protein C-terminus regulates autophagy and exosome biogenesis of pancreatic cancer through metabolic pathways.
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DOI：
10.1371/journal.pone.0114409
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Mukhopadhyay D
中科院分区：
文献类型：
--
作者：
Bhattacharya S;Pal K;Sharma AK;Dutta SK;Lau JS;Yan IK;Wang E;Elkhanany A;Alkharfy KM;Sanyal A;Patel TC;Chari ST;Spaller MR;Mukhopadhyay D
GAIP相互作用蛋白C末端（GIPC）在多种生理和疾病状态中发挥重要作用。在本研究中，我们已经确定了GIPC作为自噬和细胞外吞途径的主要调节剂在癌症中的新作用。我们发现胰腺癌细胞中GIPC诱导的自噬的耗竭，从自噬标志物LC 3II的上调中可以明显看出。我们进一步报道GIPC通过调节外泌体的分泌、生物合成和分子组成来调节细胞运输途径。我们还确定了GIPC参与调节自噬和微泡脱落的代谢应激途径，并观察到GIPC状态决定了外泌体中细胞货物的装载。此外，我们已经显示了耐药基因ABCG 2在来自GIPC耗尽的胰腺癌细胞的外泌体中的过表达。我们还证明，从癌细胞中耗尽GIPC使它们对吉西他滨治疗敏感，这是一种可以作为克服癌症耐药性的潜在治疗策略进行探索的途径。
GAIP interacting protein C terminus (GIPC) is known to play an important role in a variety of physiological and disease states. In the present study, we have identified a novel role for GIPC as a master regulator of autophagy and the exocytotic pathways in cancer. We show that depletion of GIPC-induced autophagy in pancreatic cancer cells, as evident from the upregulation of the autophagy marker LC3II. We further report that GIPC regulates cellular trafficking pathways by modulating the secretion, biogenesis, and molecular composition of exosomes. We also identified the involvement of GIPC on metabolic stress pathways regulating autophagy and microvesicular shedding, and observed that GIPC status determines the loading of cellular cargo in the exosome. Furthermore, we have shown the overexpression of the drug resistance gene ABCG2 in exosomes from GIPC-depleted pancreatic cancer cells. We also demonstrated that depletion of GIPC from cancer cells sensitized them to gemcitabine treatment, an avenue that can be explored as a potential therapeutic strategy to overcome drug resistance in cancer.
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影响因子：
21.3
作者：
通讯作者：
--
影响因子：
9.7
作者：
Choi, Ji Seung;Paek, A. Rome;You, Hye Jin
通讯作者：
You, Hye Jin
影响因子：
11.2
作者：
Muders, Michael H.;Dutta, Shamit K.;Mukhopadhyay, Debabrata
通讯作者：
Mukhopadhyay, Debabrata
DOI：
10.1126/science.1236566
发表时间：
2013-07-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kang SA;Pacold ME;Cervantes CL;Lim D;Lou HJ;Ottina K;Gray NS;Turk BE;Yaffe MB;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
5.4
作者：
Kumar, Sravanth Hindupur;Rangarajan, Annapoorni
通讯作者：
Rangarajan, Annapoorni