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Page 8 of 16 Nagayama. J Cancer Metastasis Treat 2021;7:6 I http://dx.doi.org/10.20517/2394-4722.2020.114

Table 1. Summary of the articles reporting pro-proliferative/tumorigenic action of autophagy
TC cell lines used * The effects on cell growth/ The effects of autophagy Ref.
survival inhibition
Autophagy inhibitors
CQ 8505C (BRAF V600E , TERT 250C>T , Inhibition of cell growth, colony [63,68,69]
and p53 R248G ), FTC133 formation and Induction of
(PTEN R130Ter and TERT 228C>T ) apoptosis
BCPAP (BRAF V600E ) and TPC1
(RET/PTC1 and TERT 228C>T )
3-MA BCPAP Inhibition of cell growth [67]
ATG5 KD 8505C and FTC133 Induction of apoptosis [68]
ATG7 KD BCPAP and TPC1 Induction of apoptosis [63,69]
Autophagy stimulators
BANCR IHH-4 (BRAF V600E and Stimulation of cell survival and Inhibition of cell growth and [58]
TERT 228C>T ) proliferation induction of apoptosis by 3-MA
LAMP2A K1 (BRAF V600E and TERT 228C>T ), Induction of chaperon-mediated Suppression of tumor cell [64]
#
W3 and TPC1 autophagy and promotion of proliferation and migration by
tumor cell proliferation and LAMP2A shRNA
migration
Sorafenib 8505C and FTC133 Inhibition of cell growth and Augmentation of sorafenib- [68]
Induction of apoptosis induced cell growth inhibition
and apoptosis by ATG5 siRNA
and CQ
Vemurafenib BCPAP, FRO and 8505C Induction of cell death (relatively Sensitization to vemurafenib- [70,76]
resistant) induction of cell death by HCQ
and ATG5 siRNA
Apatinib K1, KTC-1, KHM-5M (BRAF V600E , Induction of cell growth arrest Enhancement of apatinib- [71,72]
TERT 228C>T , and p53 R280T ) and and apoptosis induced apoptosis by HCQ,
C643 (H-RAS G13R ) 3-MA and ATG5 siRNA
CZ415 TPC1 Induction of cell death and Sensitization to CZ415-induced [73]
inhibition of colony formation cytotoxicity by 3-MA and
BECLIN-1 shRNA
Radiation SW-579 (HTB-107) Induction of apoptosis Enhancement of radiation- [74]
induced apoptosis by 3-MA and
BECLIN-1 siRNA
Cisplatin TPC1, 8305C and SW1736 Induction of cell death Sensitization to cisplatin-induced [80,81]
(BRAF V600E , TERT 228C>T , and TP53 cell death by 3-MA, CQ, miR-
Q192Te r) 144 and miR30d (a BECLIN-1
expression suppressor)
Flavokawain B WRO (BRAF V600E ) and TPC1 Induction of apoptosis and Sensitization to flavokawain [82]
mitochondrial dysfunction B-induced apoptosis by 3-MA,
CQ and BECLIN-1 siRNA
#
EBSS-induced FRO , KTC-1 (BRAF V600E and A slight cell death An increase in apoptotic cell [83]
starvation TERT 250C>T ) and KTC-3 # death by autophagy inhibitors
(BAG3 and 3-MA)
TERT BCPAP and TPC1 Increases in cell proliferation, An increase in apoptosis and [63]
migration and invasion, and a decreases in cell proliferation,
decrease in apoptosis migration and invasion by TERT
shRNA
CQ: chloroquine; 3-MA: 3-methyladenine; EBSS: Earle’s Balanced Salt Solution; BANCR: BRAF-activated lncRNA; LAMP2A: lysosome-
associated membrane protein type 2A; BAG3: Bcl-2-associated athanogene 3; TERT: telomerase reverse transcriptase. *genotypes are
from https://web.expasy.org/cellosaurus/ and [112] #
; genotypes not reported

Autophagy inducers so far reported to show the pro-survival/proliferative effect of autophagy include
[58]
[64]
BANCR , LAMP2A , tyrosine kinase inhibitors [sorafenib (a pan-tyrosine kinase inhibitor) and
[73]
vemurafenib (a BRAF inhibitor)]) [68,70,76] , apatinib (a VEGF2 inhibitor) [71,72] , CZ415 (an mTOR inhibitor) ,
[83]
[74]
radiation , cisplatin [80,81] , flavokawain B Earle’s Balanced Salt Solution-induced starvation , and
[82]
[63]
TERT [Table 1]. NOTE - among them, some data are not convincing. For example: (1) although the
authors interpret their data showing augmentation of sorafenib-induced apoptosis by ATG5 KD in thyroid
cancer cell lines 8505C and FTC133 as indicating the pro-survival effect of autophagy, sorafenib and
ATG5 KD individually induced apoptosis and the effect of their combination look merely additive (or
[68]
[73]
less than additive) ; (2) autophagic activity was not evaluated in the CZ415 study ; and (3) only LC3-II