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. 2021 Jan 14;8:601006. doi: 10.3389/fcell.2020.601006

TABLE 2.

Associations of KL with cancer.

Cancer KL level Mechanism of KL change KL effect References
Breast cancer ↓ Cancer tissues
↓ Cell lines
Epigenetic silencing; KL variant ↓ Cell proliferation
⊣ IGF-1R/AKT/GSK-3β and ERK1/2 ↑ FGF pathway
→ Regulation of endoplasmic reticulum Ca2+ storage
Wolf et al., 2008, 2010; Rubinek et al., 2012; Dallol et al., 2015; Sinha et al., 2015; Shmulevich et al., 2020
Colorectal cancer ↓ Cancer tissues
↓ Cell lines
Epigenetic silencing; miR-15b; NF-κB and IGF-1R activity; KL variant ↓ Cell survival; proliferation
↓ Tumor growth; weight; volume ↑ Cell cycle arrest ↑ Apoptosis
⊣ IGF-1R/PI3K/AKT
⊣ ERK and HIF-1α
⊣ NF-κB
⊣ Wnt3a/β-catenin signaling
Gan et al., 2011; Pan et al., 2011; Li et al., 2014, 2016, 2018; Yang et al., 2014; Bordonaro and Lazarova, 2015; Perveez et al., 2015; Arbel Rubinstein et al., 2019; Liu et al., 2019; Xie et al., 2019, 2020; Kamal et al., 2020; Son et al., 2020
Lung cancer ↓ Cancer tissues
↓ Cell lines
miR-10b; Ras8 activity ↓ Cell proliferation; growth; invasiveness; migration ↑ Apoptosis
⊣ IGF-1R/AKT
⊣ Wnt3a/β-catenin signaling
↓ IL-6 and IL-8
→ Sensitizes for cisplatin via PI3K/AKT or autophagy
Chen et al., 2010, 2012, 2016, 2019; Wang X. et al., 2011, Wang et al., 2013; Huang et al., 2015; Chen B. et al., 2018
Hepatocellular cancer ↓ Cancer tissues
↓ Cell lines
Epigenetic silencing ↓ Colony formation; proliferation; migration; invasion ↑ Apoptosis; autophagy
⊣ Wnt/β-catenin signaling
⊣ IGF-1R/AKT/ERK ↑ VEGFR2/PAK1 →↑ migration; invasion
Chen et al., 2013; Shu et al., 2013; Xie et al., 2013b; Sun et al., 2015; Tang et al., 2016b
Squamous cell carcinoma ↓ Cancer tissues Epigenetic silencing N-cadherin
→ Regulation of EMT
Adhikari et al., 2017; Ibi et al., 2017
Pancreatic cancer ↓ Cancer tissues
↓ Cell lines
Epigenetic silencing; miR-199a ↓ Colony size and number; tumor growth ↑ Chemotherapeutic effects
⊣ IGF-1R/AKT/ERK1/2
⊣ mTOR
⊣ FGF2
Abramovitz et al., 2011; Jiang et al., 2014; Zhang et al., 2020
Gastric carcinoma ↓ Cancer tissues
↓ Cell lines
Epigenetic silencing; miR-199a ↓ Growth
⊣ IGF-1R/PI3K/mTOR
⊣ ERK1/2 ↑ Apoptosis
Wang L. et al., 2011; Xie et al., 2013a; He et al., 2014
Prostate cancer ↓ Cell lines Epigenetic silencing; KL SNP Kim et al., 2014b; Seo et al., 2017
Renal cell carcinoma ↓ Cancer tissues
↓ Cell lines
↓ Cell proliferation; migration; invasion; motility; EMT
⊣ IGF-1R
⊣ PI3K/AKT/GSK-3β/Snail
⊣ EGF-1 dependent p38MAPK activation
Zhu et al., 2013; Gigante et al., 2015; Kim et al., 2016; Dehghani et al., 2018
Ovarian cancer ↓ Cancer tissues
↓ Cell lines
↓ Cell proliferation
↓ Tumor growth and tumor-associated inflammation
⊣ IGF-1/ERK1/2
Lojkin et al., 2015; Yan et al., 2017
Melanoma ↓ Aged cells PPARγ; HMGB1 and NF-κB activity ↓ Cell motility
⊣ Wnt5a-mediated filamin A cleavage
Camilli et al., 2011; Xie et al., 2016; Behera et al., 2017
Thyroid cancer ↓ Cancer tissues ↓ Cell proliferation ↑ Apoptosis
⊣ Stanniocalcin-1
Dai et al., 2016; Pawlikowski et al., 2019
Urothelial carcinoma of the bladder ↓ High- grade cancer tissues Hori et al., 2016
Glioblastoma multiforme Epigenetic silencing ↓ Cell viability Peshes-Yeloz et al., 2019
Cervical carcinoma ↓ Cancer tissues
↓ Cell lines
Epigenetic silencing ↓ EMT
⊣ Wnt/β-catenin signaling
Lee et al., 2010; Chang et al., 2012
Dedifferentiated liposarcoma ↓ Cancer tissues ↓ Cell proliferation ↑ Apoptosis
→ Sensitizes to ER stress
⊣ IGF-1–induced Ca2+ and ERK1/2 signaling
Delcroix et al., 2018
T-cell lymphoma and diffuse large B-cell lymphoma ↓ Cancer tissues
↓ Cell lines
↓ Cell proliferation ↑ Apoptosis
⊣ IGF-1R/AKT/ERK1/2
Zhou et al., 2017a,b