PMID- 32860290
OWN - NLM
STAT- MEDLINE
DCOM- 20201221
LR  - 20210110
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 111
IP  - 11
DP  - 2020 Nov
TI  - Chaperone-mediated autophagy receptor modulates tumor growth and chemoresistance 
      in non-small cell lung cancer.
PG  - 4154-4165
LID - 10.1111/cas.14629 [doi]
AB  - Chaperone-mediated autophagy (CMA) is a lysosomal degradation pathway of 
      selective soluble proteins. Lysosome-associated membrane protein type 2a (LAMP2A) 
      is the key receptor protein of CMA; downregulation of LAMP2A leads to CMA 
      blockade. Although CMA activation has been involved in cancer growth, CMA status 
      and functions in non-small cell lung cancer (NSCLC) by focusing on the roles in 
      regulating chemosensitivity remain to be clarified. In this study, we found that 
      LAMP2A expression is elevated in NSCLC cell lines and patient's tumors, 
      conferring poor survival and platinum resistance in NSCLC patients. LAMP2A 
      knockdown in NSCLC cells suppressed cell proliferation and colony formation and 
      increased the sensitivity to chemotherapeutic drugs in vitro. Furthermore, we 
      found that intrinsic apoptosis signaling is the mechanism of cell death involved 
      with CMA blockade. Remarkably, LAMP2A knockdown repressed tumorigenicity and 
      sensitized the tumors to cisplatin treatment in NSCLC-bearing mice. Our 
      discoveries suggest that LAMP2A is involved in the regulation of cancer malignant 
      phenotypes and represents a promising new target against chemoresistant NSCLC.
CI  - (c) 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd 
      on behalf of Japanese Cancer Association.
FAU - Ichikawa, Akihiro
AU  - Ichikawa A
AD  - Department of Internal Medicine, Division of Respiratory Diseases, The Jikei 
      University School of Medicine, Tokyo, Japan.
FAU - Fujita, Yu
AU  - Fujita Y
AUID- ORCID: 0000-0002-8916-7303
AD  - Department of Internal Medicine, Division of Respiratory Diseases, The Jikei 
      University School of Medicine, Tokyo, Japan.
AD  - Division of Molecular and Cellular Medicine, National Cancer Center Research 
      Institute, Tokyo, Japan.
FAU - Hosaka, Yusuke
AU  - Hosaka Y
AD  - Department of Internal Medicine, Division of Respiratory Diseases, The Jikei 
      University School of Medicine, Tokyo, Japan.
FAU - Kadota, Tsukasa
AU  - Kadota T
AD  - Department of Internal Medicine, Division of Respiratory Diseases, The Jikei 
      University School of Medicine, Tokyo, Japan.
AD  - Division of Molecular and Cellular Medicine, National Cancer Center Research 
      Institute, Tokyo, Japan.
FAU - Ito, Akihiko
AU  - Ito A
AD  - Department of Internal Medicine, Division of Respiratory Diseases, The Jikei 
      University School of Medicine, Tokyo, Japan.
FAU - Yagishita, Shigehiro
AU  - Yagishita S
AD  - Division of Molecular Pharmacology, National Cancer Center Research Institute, 
      Tokyo, Japan.
FAU - Watanabe, Naoaki
AU  - Watanabe N
AD  - Department of Internal Medicine, Division of Respiratory Diseases, The Jikei 
      University School of Medicine, Tokyo, Japan.
AD  - Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo, 
      Japan.
FAU - Fujimoto, Shota
AU  - Fujimoto S
AD  - Department of Internal Medicine, Division of Respiratory Diseases, The Jikei 
      University School of Medicine, Tokyo, Japan.
FAU - Kawamoto, Hironori
AU  - Kawamoto H
AD  - Department of Internal Medicine, Division of Respiratory Diseases, The Jikei 
      University School of Medicine, Tokyo, Japan.
FAU - Saito, Nayuta
AU  - Saito N
AD  - Department of Internal Medicine, Division of Respiratory Diseases, The Jikei 
      University School of Medicine, Tokyo, Japan.
FAU - Yoshida, Masahiro
AU  - Yoshida M
AD  - Department of Internal Medicine, Division of Respiratory Diseases, The Jikei 
      University School of Medicine, Tokyo, Japan.
FAU - Hashimoto, Mitsuo
AU  - Hashimoto M
AD  - Department of Internal Medicine, Division of Respiratory Diseases, The Jikei 
      University School of Medicine, Tokyo, Japan.
FAU - Minagawa, Shunsuke
AU  - Minagawa S
AD  - Department of Internal Medicine, Division of Respiratory Diseases, The Jikei 
      University School of Medicine, Tokyo, Japan.
FAU - Hara, Hiromichi
AU  - Hara H
AD  - Department of Internal Medicine, Division of Respiratory Diseases, The Jikei 
      University School of Medicine, Tokyo, Japan.
FAU - Motoi, Noriko
AU  - Motoi N
AUID- ORCID: 0000-0001-7098-3311
AD  - Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, 
      Japan.
FAU - Yamamoto, Yusuke
AU  - Yamamoto Y
AUID- ORCID: 0000-0002-5262-8479
AD  - Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo, 
      Japan.
FAU - Ochiya, Takahiro
AU  - Ochiya T
AUID- ORCID: 0000-0002-0776-9918
AD  - Division of Molecular and Cellular Medicine, National Cancer Center Research 
      Institute, Tokyo, Japan.
AD  - Department of Molecular and Cellular Medicine, Institute of Medical Science, 
      Tokyo Medical University, Tokyo, Japan.
FAU - Araya, Jun
AU  - Araya J
AD  - Department of Internal Medicine, Division of Respiratory Diseases, The Jikei 
      University School of Medicine, Tokyo, Japan.
FAU - Kuwano, Kazuyoshi
AU  - Kuwano K
AD  - Department of Internal Medicine, Division of Respiratory Diseases, The Jikei 
      University School of Medicine, Tokyo, Japan.
LA  - eng
GR  - JP17K09672/Japan Society for the Promotion of Science KAKENHI/
GR  - JP17K09673/Japan Society for the Promotion of Science KAKENHI/
GR  - JP17K09674/Japan Society for the Promotion of Science KAKENHI/
GR  - JP18K08158/Japan Society for the Promotion of Science KAKENHI/
GR  - JP19K17649/Japan Society for the Promotion of Science KAKENHI/
GR  - JP19K08612/Japan Society for the Promotion of Science KAKENHI/
GR  - JP19K08632/Japan Society for the Promotion of Science KAKENHI/
GR  - National Cancer Center Research and Development Fund, Japan/
PT  - Journal Article
DEP - 20200907
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (LAMP2 protein, human)
RN  - 0 (Lysosomal-Associated Membrane Protein 2)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Biomarkers, Tumor
MH  - Carcinoma, Non-Small-Cell Lung/drug therapy/*metabolism/mortality/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - *Drug Resistance, Neoplasm
MH  - Gene Expression
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Immunohistochemistry
MH  - Lung Neoplasms/drug therapy/*metabolism/mortality/pathology
MH  - Lysosomal-Associated Membrane Protein 2/genetics/*metabolism
MH  - Lysosomes/*metabolism
MH  - Prognosis
MH  - Proteolysis
MH  - *Signal Transduction
PMC - PMC7648026
OTO - NOTNLM
OT  - LAMP2A
OT  - apoptosis
OT  - chaperone-mediated autophagy
OT  - chemoresistance
OT  - lung cancer
COIS- The authors declare that no conflict of interest exists with regard to this 
      study.
EDAT- 2020/08/30 06:00
MHDA- 2020/12/22 06:00
PMCR- 2020/11/01
CRDT- 2020/08/30 06:00
PHST- 2020/04/29 00:00 [received]
PHST- 2020/08/12 00:00 [revised]
PHST- 2020/08/16 00:00 [accepted]
PHST- 2020/08/30 06:00 [pubmed]
PHST- 2020/12/22 06:00 [medline]
PHST- 2020/08/30 06:00 [entrez]
PHST- 2020/11/01 00:00 [pmc-release]
AID - CAS14629 [pii]
AID - 10.1111/cas.14629 [doi]
PST - ppublish
SO  - Cancer Sci. 2020 Nov;111(11):4154-4165. doi: 10.1111/cas.14629. Epub 2020 Sep 7.