Abstract
Introduction: Abundant studies have disclosed that proteins can function as pivotal tumor promoters or suppressors in cancers’ progression. This work was planned to investigate the regulatory function of N-myristoyltransferase-1 (NMT1) on non-small cell lung cancer (NSCLC) and the underlying molecular mechanisms. Methods: The self-renewal abilities were assessed through a spheroid-formation assay. The tumorigenic abilities were examined through nude mice in vivo assay. The proteins’ expression was measured through Western blot. The NMT1 protein expression in tumor tissues was measured through an IHC assay. The cell migration and invasion was confirmed through a transwell assay. The IC50 was verified through a CCK-8 assay. The NMT1 mRNA expression in NSCLC tissues was detected through RT-qPCR. Results: It was demonstrated that NMT1 exhibited higher expression in spheroid cells. Additionally, NMT1 facilitated the stemness in NSCLC. It was also found that NMT1 accelerated NSCLC tumor metastasis and the resistance to cisplatin. Moreover, NMT1 activated the PI3K/AKT pathway to facilitate stemness in NSCLC. NMT1 was also higher in tumor tissues of NSCLC patients and resulted in a poor survival rate. Conclusion: NMT1 enhanced the stemness of NSCLC cells by activating the PI3K/AKT pathway. This discovery suggested that NMT1 may be a valid therapeutic biomarker for NSCLC.
Journal Section:
Research Article
References
1.
Nanavaty
P
, Alvarez
MS
, Alberts
WM
. Lung cancer screening: advantages, controversies, and applications
. Cancer Control
. 2014 Jan
;21
(1
):9
–14
.2.
Mao
Y
, Yang
D
, He
J
, Krasna
MJ
. Epidemiology of lung cancer
. Surg Oncol Clin N Am
. 2016 Jul
;25
(3
):439
–45
.3.
Herbst
RS
, Morgensztern
D
, Boshoff
C
. The biology and management of non-small cell lung cancer
. Nature
. 2018 Jan 24
;553
(7689
):446
–54
.4.
Naylor
EC
, Desani
JK
, Chung
PK
. Targeted therapy and immunotherapy for lung cancer
. Surg Oncol Clin N Am
. 2016 Jul
;25
(3
):601
–9
.5.
Duma
N
, Santana-Davila
R
, Molina
JR
. Non-small cell lung cancer: epidemiology, screening, diagnosis, and treatment
. Mayo Clin Proc
. 2019 Aug
;94
(8
):1623
–40
.6.
Arbour
KC
, Riely
GJ
. Systemic therapy for locally advanced and metastatic non-small cell lung cancer: a review
. JAMA
. 2019 Aug 27
;322
(8
):764
–74
.7.
Yu
Y
, He
J
. Molecular classification of non-small-cell lung cancer: diagnosis, individualized treatment, and prognosis
. Front Med
. 2013 Jun
;7
(2
):157
–71
.8.
Nie
X
, Liu
H
, Ye
W
, Wei
X
, Fan
L
, Ma
H
, . LRP5 promotes cancer stem cell traits and chemoresistance in colorectal cancer
. J Cell Mol Med
. 2022 Feb
;26
(4
):1095
–112
.9.
Xie
Q
, Zhao
S
, Liu
W
, Cui
Y
, Li
F
, Li
Z
, . YBX1 enhances metastasis and stemness by transcriptionally regulating MUC1 in lung adenocarcinoma
. Front Oncol
. 2021
;11
:702491
.10.
Liu
S
, Bu
X
, Kan
A
, Luo
L
, Xu
Y
, Chen
H
, . SP1-induced lncRNA DUBR promotes stemness and oxaliplatin resistance of hepatocellular carcinoma via E2F1-CIP2A feedback
. Cancer Lett
. 2022 Mar 1
;528
:16
–30
.11.
Mei
J
, Zhu
C
, Pan
L
, Li
M
. MACC1 regulates the AKT/STAT3 signaling pathway to induce migration, invasion, cancer stemness, and suppress apoptosis in cervical cancer cells
. Bioengineered
. 2022 Jan
;13
(1
):61
–70
.12.
Wang
X
, He
H
, Rui
W
, Zhang
N
, Zhu
Y
, Xie
X
. TRIM38 triggers the uniquitination and degradation of glucose transporter type 1 (GLUT1) to restrict tumor progression in bladder cancer
. J Transl Med
. 2021 Dec 14
;19
(1
):508
.13.
Meinnel
T
, Dian
C
, Giglione
C
. Myristoylation, an ancient protein modification mirroring eukaryogenesis and evolution
. Trends Biochem Sci
. 2020 Jul
;45
(7
):619
–32
.14.
Martin
DD
, Beauchamp
E
, Berthiaume
LG
. Post-translational myristoylation: fat matters in cellular life and death
. Biochimie
. 2011 Jan
;93
(1
):18
–31
.15.
Wang
B
, Dai
T
, Sun
W
, Wei
Y
, Ren
J
, Zhang
L
, . Protein N-myristoylation: functions and mechanisms in control of innate immunity
. Cell Mol Immunol
. 2021 Apr
;18
(4
):878
–88
.16.
O'Callaghan
DW
, Haynes
LP
, Burgoyne
RD
. High-affinity interaction of the N-terminal myristoylation motif of the neuronal calcium sensor protein hippocalcin with phosphatidylinositol 4,5-bisphosphate
. Biochem J
. 2005 Oct 15
;391
(Pt 2
):231
–8
.17.
Chen
W
, Salari
H
, Taylor
MC
, Jost
R
, Berkowitz
O
, Barrow
R
, . NMT1 and NMT3 N-methyltransferase activity is critical to lipid homeostasis, morphogenesis, and reproduction
. Plant Physiol
. 2018 Aug
;177
(4
):1605
–28
.18.
Selvakumar
P
, Kumar
S
, Dimmock
JR
, Sharma
RK
. NMT1 (N-myristoyltransferase 1)
. Atlas Genet Cytogenet Oncol Haematol
. 2011 Jan 7
;15
(7
):570
–5
.19.
Mackey
JR
, Lai
J
, Chauhan
U
, Beauchamp
E
, Dong
WF
, Glubrecht
D
, . N-myristoyltransferase proteins in breast cancer: prognostic relevance and validation as a new drug target
. Breast Cancer Res Treat
. 2021 Feb
;186
(1
):79
–87
.20.
Deng
L
, Gao
X
, Liu
B
, He
X
, Xu
J
, Qiang
J
, . NMT1 inhibition modulates breast cancer progression through stress-triggered JNK pathway
. Cell Death Dis
. 2018 Nov 16
;9
(12
):1143
.21.
Sun
Y
, Guan
Z
, Sheng
Q
, Duan
W
, Zhao
H
, Zhou
J
, . N-myristoyltransferase-1 deficiency blocks myristoylation of LAMTOR1 and inhibits bladder cancer progression
. Cancer Lett
. 2022 Mar 31
;529
:126
–38
.22.
Ma
X
, Yuan
Y
, Lu
J
, Li
M
, Yu
Y
, Liu
J
, . Long noncoding RNA ANCR promotes migration, invasion, EMT progress and stemness of nasopharyngeal carcinoma cells via the miR-4731-5p/NMT1 axis
. Pathol Res Pract
. 2021 Aug
;224
:153540
.23.
Kim
S
, Alsaidan
OA
, Goodwin
O
, Li
Q
, Sulejmani
E
, Han
Z
, . Blocking myristoylation of Src inhibits its kinase activity and suppresses prostate cancer progression
. Cancer Res
. 2017 Dec 15
;77
(24
):6950
–62
.24.
Zhu
G
, Wang
F
, Li
H
, Zhang
X
, Wu
Q
, Liu
Y
, . N-Myristoylation by NMT1 Is POTEE-dependent to stimulate liver tumorigenesis via differentially regulating ubiquitination of targets
. Front Oncol
. 2021
;11
:681366
.25.
Dawood
S
, Austin
L
, Cristofanilli
M
. Cancer stem cells: implications for cancer therapy
. Oncology
. 2014 Dec
;28
(12
):1101
–7
, 1110.26.
Nassar
D
, Blanpain
C
. Cancer stem cells: basic concepts and therapeutic implications
. Annu Rev Pathol
. 2016 May 23
;11
:47
–76
.27.
Yuan
Z
, Xiu
C
, Liu
D
, Zhou
G
, Yang
H
, Pei
R
, . Long noncoding RNA LINC-PINT regulates laryngeal carcinoma cell stemness and chemoresistance through miR-425-5p/PTCH1/SHH axis
. J Cell Physiol
. 2019 Dec
;234
(12
):23111
–22
.28.
Huang
Z
, Shen
G
, Gao
J
. CDK1 promotes the stemness of lung cancer cells through interacting with Sox2
. Clin Transl Oncol
. 2021 Sep
;23
(9
):1743
–51
.29.
Chi
J
, Zhang
H
, Hu
J
, Song
Y
, Li
J
, Wang
L
, . AGR3 promotes the stemness of colorectal cancer via modulating Wnt/β-catenin signalling
. Cell Signal
. 2020 Jan
;65
:109419
.30.
Wu
X
, Wang
Y
, Zhong
W
, Cheng
H
, Tian
Z
. RNA binding protein RNPC1 suppresses the stemness of human endometrial cancer cells via stabilizing MST1/2 mRNA
. Med Sci Monit
. 2020 Feb 23
;26
:e921389
.31.
Xu
L
, Zhang
X
, Wang
Z
, Zhao
X
, Zhao
L
, Hu
Y
. Kinesin family member 2A promotes cancer cell viability, mobility, stemness, and chemoresistance to cisplatin by activating the PI3K/AKT/VEGF signaling pathway in non-small cell lung cancer
. Am J Transl Res
. 2021
;13
(4
):2060
–76
.32.
Yang
Y
, Zhang
T
, Wu
L
. TUFT1 facilitates metastasis, stemness, and vincristine resistance in colorectal cancer via activation of PI3K/AKT pathway
. Biochem Genet
. 2021 Aug
;59
(4
):1018
–32
.33.
Yang
Z
, Zhang
C
, Qi
W
, Cui
Y
, Xuan
Y
. GLI1 promotes cancer stemness through intracellular signaling pathway PI3K/Akt/NFκB in colorectal adenocarcinoma
. Exp Cell Res
. 2018 Dec 15
;373
(1–2
):145
–54
.34.
Gao
XF
, He
HQ
, Zhu
XB
, Xie
SL
, Cao
Y
. LncRNA SNHG20 promotes tumorigenesis and cancer stemness in glioblastoma via activating PI3K/Akt/mTOR signaling pathway
. Neoplasma
. 2019 Jul 23
;66
(4
):532
–42
.35.
Pan
S
, Sun
Y
, Sui
D
, Yang
T
, Fu
S
, Wang
J
, . Lobaplatin promotes radiosensitivity, induces apoptosis, attenuates cancer stemness and inhibits proliferation through PI3K/AKT pathway in esophageal squamous cell carcinoma
. Biomed Pharmacother
. 2018 Jun
;102
:567
–74
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