The Journal of Practical Medicine >
Role and potential mechanisms of p62/SQSTM1 on migration and metastasis of non⁃small cell lung cancer
Received date: 2023-10-01
Online published: 2024-01-24
Objective To investigate the effect and regulatory mechanism of autophagy related multifunctional protein p62/SQSTM1 on biological behavior in non?small cell lung cancer （NSCLC）. Methods RT?qPCR was used to detect the expression of p62 in normal lung cells and NSCLC cells. CCK?8， wound?healing and Transwell assays were used to detect the effects of inhibition and promotion of p62 expression on the proliferation， migration and invasion in NSCLC cells. Western blotting was used to detect the effects of inhibition and promotion of p62 expression on the expression of apoptosis?related proteins （Bcl?2 and Bax） and autophagy?related proteins （ATG5 and Becline1） in NSCLC cells. A nude mouse transplantation tumor experiment was used to detect the effect of inhibiting p62 expression on the tumor volume and mass of NSCLC cells in vivo. Results Compared with that in normal lung cells， the expression level of p62 in A549 cells was the highest. Cell function experiments in vitro showed that inhibition of p62 expression reduced the abilities of proliferation， migration and invasion in A549 cells， and suppressed autophagy and induced apoptosis. Consistently， p62 overexpression has the opposite effects. In addition， animal experiments in vivo showed that inhibition of p62 expression decreased the tumor volume and mass of tumor?bearing mice. Conclusion p62 could promote the growth of NSCLC A549 cell in vivo and in vitro by modulating autophagy.
Key words： non?small cell lung cancer; autophagy; proliferation; migration; invasion
Xue MA , Shihui. ZHOU . Role and potential mechanisms of p62/SQSTM1 on migration and metastasis of non⁃small cell lung cancer[J]. The Journal of Practical Medicine, 2024 , 40(1) : 13 -18 . DOI: 10.3969/j.issn.1006-5725.2024.01.003
| 1 | FRICK C， RUMGAY H， VIGNAT J， et al. Quantitative estimates of preventable and treatable deaths from 36 cancers worldwide： a population-based study［J］. Lancet Glob Health， 2023，11（11）：e1700-e1712. |
| 2 | SMIDA T， BRUNO T C， STABILE L P. Influence of Estrogen on the NSCLC Microenvironment： A Comprehensive Picture and Clinical Implications［J］. Front Oncol， 2020，10：137. |
| 3 | LU S， WU L， JIAN H， et al. Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy （ORIENT-31）： first interim results from a randomised， double-blind， multicentre， phase 3 trial［J］. Lancet Oncol， 2022，23（9）：1167-1179. |
| 4 | CHAUDHRY G E， AKIM A M， SUNG Y Y， et al. Cancer and Apoptosis［J］. Methods Mol Biol， 2022，2543：191-210. |
| 5 | RUSSELL R C， GUAN K L. The multifaceted role of autophagy in cancer［J］. EMBO J， 2022，41（13）：e110031. |
| 6 | ZHANG Z， SHI J， NICE E C， et al. The Multifaceted Role of Flavonoids in Cancer Therapy： Leveraging Autophagy with a Double-Edged Sword［J］. Antioxidants （Basel）， 2021，10（7）：1138. |
| 7 | VARGAS J N S， HAMASAKI M， KAWABATA T， et al. The mechanisms and roles of selective autophagy in mammals［J］. Nat Rev Mol Cell Biol， 2023，24（3）：167-185. |
| 8 | TAN C T， SOH N J H， CHANG H C， et al. p62/SQSTM1 in liver diseases： the usual suspect with multifarious identities［J］. FEBS J， 2023，290（4）：892-912. |
| 9 | ZENG X， ZHANG Y D， MA R Y， et al. Activated Drp1 regulates p62-mediated autophagic flux and aggravates inflammation in cerebral ischemia-reperfusion via the ROS-RIP1/RIP3-exosome axis［J］. Mil Med Res， 2022，9（1）：25. |
| 10 | KUMAR A V， MILLS J， LAPIERRE L R. Selective Autophagy Receptor p62/SQSTM1， a Pivotal Player in Stress and Aging［J］. Front Cell Dev Biol， 2022，10：793328. |
| 11 | 陈秀英， 于莉， 周君阳， 等. p62基因敲除后食管鳞状细胞癌 EC109 细胞生物学行为变化［J］. 山东医药， 2020， 60（2）： 10-13. |
| 12 | LINARES J F， CID-DIAZ T， DURAN A， et al. The lactate-NAD+ axis activates cancer-associated fibroblasts by downregulating p62［J］. Cell Rep， 2022，39（6）：110792. |
| 13 | FAN X， HUANG T， TONG Y， et al. p62 works as a hub modulation in the ageing process［J］. Ageing Res Rev， 2022，73：101538. |
| 14 | KOMATSU M. p62 bodies： Phase separation， NRF2 activation， and selective autophagic degradation［J］. IUBMB Life， 2022，74（12）：1200-1208. |
| 15 | CHEN X， LI J， KANG R， et al. Ferroptosis： machinery and regulation［J］. Autophagy， 2021，17（9）：2054-2081. |
| 16 | BERGMANN R， GULOTTA G， ANDREONI F， et al. The group A Streptococcus interleukin-8 protease SpyCEP promotes bacterial intracellular survival by evasion of autophagy［J］. Infect Microbes Dis， 2022，4（3）：116-123. |
| 17 | HU Y J， ZHONG J T， GONG L， et al. Autophagy-Related Beclin 1 and Head and Neck Cancers［J］. Onco Targets Ther， 2020，13：6213-6227. |
| 18 | WHITE J， SUKLABAIDYA S， et al. Multifaceted roles of TAX1BP1 in autophagy［J］. Autophagy， 2023，19（1）：44-53. |
| 19 | SOUKUP A A， BRESNICK E H. GATA2 +9.5 enhancer： from principles of hematopoiesis to genetic diagnosis in precision medicine［J］. Curr Opin Hematol， 2020，27（3）：163-171. |
| 20 | QIN S， GENG H， WANG G， et al. Suffruticosol C-Mediated Autophagy and Cell Cycle Arrest via Inhibition of mTORC1 Signaling［J］. Nutrients， 2022，14（23）：5000. |
| 21 | YANG K， LUAN L， LI X， et al. ERK inhibition in glioblastoma is associated with autophagy activation and tumorigenesis suppression［J］. J Neurooncol， 2022，156（1）：123-137. |
| 22 | SCHWERTHEIM S， K?LSCH J， JASTROW H， et al. Characterization of two types of intranuclear hepatocellular inclusions in NAFLD［J］. Sci Rep， 2020，10（1）：16533. |
| 23 | YANG S， LI F， LU S， et al. Ginseng root extract attenuates inflammation by inhibiting the MAPK/NF-κB signaling pathway and activating autophagy and p62-Nrf2-Keap1 signaling in vitro and in vivo［J］. J Ethnopharmacol， 2022，283：114739. |
| 24 | YU T， YANG X， FU Q， et al. TRIM11 attenuates Treg cell differentiation by p62-selective autophagic degradation of AIM2［J］. Cell Rep， 2023，42（10）：113231. |
| 25 | LIU J， LIU Y， WANG Y， et al. TMEM164 is a new determinant of autophagy-dependent ferroptosis［J］. Autophagy， 2023，19（3）：945-956. |
/
| 〈 |
|
〉 |