High expression of IRE1 in lung adenocarcinoma is associated with a lower rate of recurrence

Sakatani, Toshio; Maemura, Kouji; Hiyama, Noriko; Amano, Yosuke; Watanabe, Kousuke; Kage, Hidenori; Fukayama, Masashi; Nakajima, Jun; Yatomi, Yutaka; Nagase, Takahide; Takai, Daiya

doi:10.1093/jjco/hyx031

Cited by 7 publications

(9 citation statements)

References 24 publications

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“…Total RNA was extracted from cultured cells or patient tumor specimens and reverse transcribed into cDNA, as described previously ( 23 ). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed using the following primers: glyceraldehyde 3-phosphate dehydrogenase (GAPDH), forward 5′-CAC CAC CAA CTG CTT AGC AC-3′ and reverse 5′-TGG CAG GTT TTC TAG ACG G-3′; GCLC, forward 5′-ACG GAG GAA CAA TGT CCG AG-3′ and reverse 5′-TAC TGA AGC GAG GGT GCT TG-3′; xCT, forward 5’-CAG GAG AAA GTG CAG CTG AA-3′ and reverse 5′-CTC CAA TGA TGG TGC CAA TG-3′; all CD44, forward 5′-TCG CTA CAG CAT CTC TCG GA-3′ and reverse 5′-TGC TGC ACA GAT GGA GTT GG-3′; and CD44v8-10, forward 5′-GAC AGA ATC CCT GCT ACC AAT A-3′ and reverse 5′-ATG TGT CTT GGT CTC CTG ATA A-3′.…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

Glutamate-cysteine ligase catalytic subunit is associated with cisplatin resistance in lung adenocarcinoma

Hiyama

Ando

Maemura

et al. 2018

Japanese Journal of Clinical Oncology

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Section: Patients Materials and Methodsmentioning

confidence: 99%

Glutamate-cysteine ligase catalytic subunit is associated with cisplatin resistance in lung adenocarcinoma

Hiyama

Ando

Maemura

et al. 2018

Japanese Journal of Clinical Oncology

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“… 45 For instance, increased expression levels of major actors of the UPR such as IRE1α, unspliced and spliced XBP1, PERK and ATF6 were observed in tissues sections from a variety of human tumors including brain, breast, gastric, kidney, liver, lung and pancreatic cancers ( Table 1 ). 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 Moreover, the chaperone GRP78 is also found overexpressed in many cancers 46 , 47 , 48 , 49 , 50 , 51 , 52 , 54 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 64 , 65 , 66 and is involved in the dissemination/metastasis of human tumors. GRP78 overexpression is associated with higher tumor grades and reduced patients’ survival.…”

Section: Upr Molecular Mechanisms and Their Functions In Cancers: Thementioning

confidence: 99%

Endoplasmic reticulum stress signaling and chemotherapy resistance in solid cancers

2017

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The unfolded protein response (UPR) is an adaptive cellular program used by eukaryotic cells to cope with protein misfolding stress. During tumor development, cancer cells are facing intrinsic (oncogene activation) and extrinsic (limiting nutrient or oxygen supply) challenges, with which they must cope to survive. Moreover, chemotherapy represents an additional extrinsic challenge that cancer cells are facing and to which they adapt in the case of resistance. As of today, resistance to chemotherapy and targeted therapies is one of the important issues that oncologists have to deal with for treating cancer patients. In this review, we first describe the key molecular mechanisms controlling the UPR and their implication in solid cancers. Then, we review the literature that connects cancer chemotherapy resistance mechanisms and activation of the UPR. Finally, we discuss the possible applications of targeting the UPR to bypass drug resistance.

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“…26 ERN2 also activates serine/threonine-protein kinase and participates in the response to EGFR-TKIs. 27,28 Our study observed that the expression of EEF1A2 was downregulated in patients with MLNM harboring EGFR 19Del mutations compared with those patients without MLNM, and conversely upregulated in patients with MLNM harboring EGFR L858R mutations, whereas the expression of ERN2 was upregulated in patients with EGFR 19Del mutations and downregulated in those with EGFR L858R mutations. The expression of ERN2 was verified with quantitative RT-PCR in these 10 patients and found to be consistent with the results from transcriptome sequencing.…”

Section: Discussionmentioning

confidence: 63%

EEF1A2 and ERN2 could potentially discriminate metastatic status of mediastinal lymph node in lung adenocarcinomas harboring EGFR 19Del/L858R mutations

Xia

Wang

et al. 2020

Thoracic Cancer

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Background: Early data has indicated that EGFR 19Del mutation and EGFR L585R mutation are two different types of non-small cell lung cancer (NSCLC). However, how the different molecular mechanisms participate in the process of mediastinal lymph node metastasis (MLNM) in lung adenocarcinoma (LA) harboring EGFR 19Del and EGFR L858R mutation remains unknown. We thus explored the genes responsible for MLNM in LA with EGFR 19Del or L858R mutation. Methods: We performed transcriptome sequencing and bioinformatics analysis from 10 patients with LA resection specimens of primary tumors. Quantitative reverse transcription-polymerase chain reaction was used to validate gene expressions. Results: There were 69 mRNAs upregulated and 100 mRNAs downregulated in five samples with MLNM compared with samples without MLN metastasis. EEF1A2 and ERN2 were observed exhibiting different expression patterns in EGFR 19Del and EGFR L858R samples with MLNM. In samples harboring EGFR 19Del mutation, the expression of EEF1A2 gene in samples with MLNM was significantly lower compared with samples without MLN metastasis, and in samples with EGFR L858R, it was significantly higher in samples with MLNM. The expression pattern of ERN2 was opposite to EEF1A2. In addition, several other genes including SLC6A11, IGHV3-48, IGHV3-43, DUSP9, and HOXA9 were also shown to be associated with invasion and metastasis and exhibited an expression pattern similar to EEF1A2 and ERN2 in EGRF 19Del and L858R mutation tumors. Conclusions: EEF1A2 and ERN2 were for the first time observed exhibiting distinct expression patterns in MLNM in lung adenocarcinomas harboring EGFR 19Del and EGFR L858R mutation by interindividual DEGs analysis.

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High expression of IRE1 in lung adenocarcinoma is associated with a lower rate of recurrence

Abstract: High expression of endoplasmic reticulum stress-related genes was observed in patients with lower stages of lung adenocarcinoma and minimal vascular invasion. High inositol-requiring kinase 1 expression was an independent predictor of recurrence-free survival.

Cited by 7 publications

References 24 publications

Glutamate-cysteine ligase catalytic subunit is associated with cisplatin resistance in lung adenocarcinoma

Glutamate-cysteine ligase catalytic subunit is associated with cisplatin resistance in lung adenocarcinoma

Endoplasmic reticulum stress signaling and chemotherapy resistance in solid cancers

EEF1A2 and ERN2 could potentially discriminate metastatic status of mediastinal lymph node in lung adenocarcinomas harboring EGFR 19Del/L858R mutations

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