Protein phosphatase 2A (PP2A): a key phosphatase in the progression of chronic obstructive pulmonary disease (COPD) to lung cancer

Table 1 Summary of PP2A related signalling pathways in lung disease

	PP2A Interaction	Upstream	Downstream	Physiological effect	Disease	Ref.
Inhibitory
CIP2A	Directly inhibits PP2A	↑EGFR	↓ERK ↑MMP1 and MMP9	ECM degradation	COPD, Lung Cancer	[28, 82]
			↓ELK-1 ↑AKT	Cell survival	Lung Cancer	[94, 95, 98, 104, 106]
			↑c-MYC	Proliferation, self-renewal and oncogenic transformation	Lung Cancer	[70, 95, 99, 103]
			↑MKK4, JNK, ATF2, c-jun	Proliferation	Lung Cancer	[36]
SET	Directly inhibits PP2A		↑AKT, cyclin D1, MMP9 ↓P27	Proliferation, ECM degradation and invasion	Lung Cancer	[34, 35]
		↑PCDH7	↑ERK, cyclin D1, MMP9 ↓P27	Proliferation, ECM degradation and invasion	Lung Cancer	[34, 35, 83]
			↑c-MYC ↓NRDG1, RIPK1	Invasion, oncogenic transformation and metastasis	Lung Cancer	[34, 113]
PME-1	Stablises inactive PP2A		↑ERK, AKT	Proliferation	Lung Cancer	[81]
MID1	Degrades PP2A-C	↑TRAIL		Fibrosis, collagen deposition, cell survival and proliferation	Asthma, Pulmonary fibrosis, Lung cancer	[116, 117]
Beneficial
Calpains	PP2A inactivates calpains		↓μ - and m-calpains	Suppression of invasion and migration, and wound healing	Lung Cancer	[123, 124]
Rho B	Rho B binds to PP2A-B55 to increase active PP2A	↑RASSF1A	↓AKT-1 ↑GEF-H1	suppression of invasion and migration	Lung Cancer	[125, 126] [128]
TTP	PP2A activates TTP	↓P38- MAPK, MK2	↓IL-6, IL-8 ↓LATS2, cyclin B1	Suppression of inflammation and proliferation.	COPD, Asthma, Lung cancer	[29,30,31]

ISSN: 1465-993X