scholarly journals JNK and Yorkie drive tumor malignancy by inducing L-amino acid transporter 1 in Drosophila

PLoS Genetics ◽  
2021 ◽  
Vol 17 (11) ◽  
pp. e1009893
Author(s):  
Bojie Cong ◽  
Mai Nakamura ◽  
Yukari Sando ◽  
Takefumi Kondo ◽  
Shizue Ohsawa ◽  
...  

Identifying a common oncogenesis pathway among tumors with different oncogenic mutations is critical for developing anti-cancer strategies. Here, we performed transcriptome analyses on two different models of Drosophila malignant tumors caused by Ras activation with cell polarity defects (RasV12/scrib-/-) or by microRNA bantam overexpression with endocytic defects (bantam/rab5-/-), followed by an RNAi screen for genes commonly essential for tumor growth and malignancy. We identified that Juvenile hormone Inducible-21 (JhI-21), a Drosophila homolog of the L-amino acid transporter 1 (LAT1), is upregulated in these malignant tumors with different oncogenic mutations and knocking down of JhI-21 strongly blocked their growth and invasion. JhI-21 expression was induced by simultaneous activation of c-Jun N-terminal kinase (JNK) and Yorkie (Yki) in these tumors and thereby contributed to tumor growth and progression by activating the mTOR-S6 pathway. Pharmacological inhibition of LAT1 activity in Drosophila larvae significantly suppressed growth of RasV12/scrib-/- tumors. Intriguingly, LAT1 inhibitory drugs did not suppress growth of bantam/rab5-/- tumors and overexpression of bantam rendered RasV12/scrib-/- tumors unresponsive to LAT1 inhibitors. Further analyses with RNA sequencing of bantam-expressing clones followed by an RNAi screen suggested that bantam induces drug resistance against LAT1 inhibitors via downregulation of the TMEM135-like gene CG31157. Our observations unveil an evolutionarily conserved role of LAT1 induction in driving Drosophila tumor malignancy and provide a powerful genetic model for studying cancer progression and drug resistance.

Author(s):  
Ran Li ◽  
Xiaocui Tang ◽  
Changqiong Xu ◽  
Yinrui Guo ◽  
Longkai Qi ◽  
...  

Background: Astroglioma is the most common primary tumor of the central nervous system. Currently, there is no effective treatment for astroglioma. In the present study, the extract (L3) from Ganoderma Lucidum (G.lucidum) was found to inhibit the growth of astroglioma U87 cells and change the expression of circular RNAs (circRNAs). One of these, including the circular NF1-419 (circNF1-419), was of interest because NF1 gene is a classic tumor suppressor gene. Objective: The functional role of circ-NF1-419 in the inhibition of astroglioma cells remains unknown. This study focuses on the role of circNF1-419 in functional abnormalities of U87 astroglioma cells and aims to elaborate on its regulatory mechanism. Methods: The circNF1-419 overexpressing U87 (U87-NF1-419) cells were constructed. We generated U87-NF1-419 to evaluate the role of circNF1-419 on cell cycle, apoptosis, proliferation, tumor growth and metabolic regulation. Finally, we used docking screening to identify compounds in G. lucidum extracts that target circ-419. Results: U87-NF1-419 can promote cell apoptosis and regulate lipid metabolism through glycerophospholipid metabolism and retrograde endocannabinoid signaling. Further examinations revealed that the expression of metabolic regulators, such as L-type voltage-operated calcium channels (L-VOCC), phospholipase C-β3 (PLCβ3), Mucin1, cationic amino acid transporter 4 (CAT4), cationic amino acid transporter 1 (CAT1) and a kinase (PRKA) anchor protein 4 (AKAP4) was inhibited, while phosphatidylserine synthase 1 (PTDSS1) was enhanced in U87-NF1-419 cells. In vivo experiments showed that circNF1-419 inhibits tumor growth in BALB/C nude mice, and enhanced AKAP4 and PTDSS1 in tumor tissues. The virtual docking screening results supported that ganosporeric acid A, ganodermatriol, ganoderic acid B and α-D-Arabinofuranosyladenine in L3 could activate circNF1-419 in astroglioma treatment. Conclusion: This study indicated that circNF1-419 could be a therapeutic target for the clinical treatment of astroglioma. L3 from Ganoderma Lucidum (G.lucidum) could inhibit astroglioma growth by activating circNF1-419.


2008 ◽  
Vol 179 (4S) ◽  
pp. 105-105
Author(s):  
Takefumi Satoh ◽  
Takeshi Sakata ◽  
Isao Okayasu ◽  
Golam Ferdous ◽  
Tomoko Tsuruta ◽  
...  

Neurosurgery ◽  
2008 ◽  
Vol 62 (2) ◽  
pp. 493-504 ◽  
Author(s):  
Keiichi Kobayashi ◽  
Akiko Ohnishi ◽  
Jutabha Promsuk ◽  
Saki Shimizu ◽  
Yoshikatsu Kanai ◽  
...  

2010 ◽  
Vol 45 (2) ◽  
pp. 93-102 ◽  
Author(s):  
Zhongxing Liang ◽  
Heidi T. Cho ◽  
Larry Williams ◽  
Aizhi Zhu ◽  
Ke Liang ◽  
...  

2022 ◽  
Vol 10 ◽  
pp. 2050313X2110679
Author(s):  
Shunsuke Yahiro ◽  
Takuya Fujimoto ◽  
Ikuo Fujita ◽  
Toshihiro Takai ◽  
Toshiko Sakuma ◽  
...  

Proximal-type epithelioid sarcoma is an aggressive malignant soft-tissue neoplasm, a “proximal” variant of epithelioid sarcoma, resistant to multimodal therapy and involved in early tumor-related death. Pertinent treatments are, therefore, continually being explored. A 24-year-old woman with nonmetastatic proximal-type epithelioid sarcoma, originating subcutaneously on the right side of the vulva, underwent surgical resection; the lesion recurred, however, leading to death 3 months after the second surgery. Here described is a case of proximal-type epithelioid sarcoma expressing L-type amino acid transporter 1 (LAT1) that transports essential amino acids and p-borono-L-phenylalanine (BPA)—the chemical compound used in boron neutron capture therapy (BNCT)—and is highly expressed in many malignant tumors. Recently, LAT1 has drawn attention, and relevant treatments have been studied—LAT1 inhibitor and BNCT. LAT1 expression in proximal-type epithelioid sarcoma may lead to cogent treatments for the disease.


2018 ◽  
Vol 293 (8) ◽  
pp. 2877-2887 ◽  
Author(s):  
Yann Cormerais ◽  
Pierre André Massard ◽  
Milica Vucetic ◽  
Sandy Giuliano ◽  
Eric Tambutté ◽  
...  

2001 ◽  
Vol 120 (5) ◽  
pp. A153-A153
Author(s):  
S MIYAMOTO ◽  
K KATO ◽  
Y ISHII ◽  
S ASAI ◽  
T NAGAISHI ◽  
...  

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