Placenta‑specific protein 8 promotes the proliferation of lung adenocarcinoma PC‑9 cells and their tolerance to an epidermal growth factor receptor tyrosine kinase inhibitor by activating the ERK signaling pathway

Abstract

Placenta-specific protein 8 (PLAC8) is a conserved protein with a molecular weight of 12.5 kDa. The specific function of this protein has not been fully elucidated, however, PLAC8 has been found to play an important tumor regulatory role in certain types of cancer, including colon, pancreatic and liver cancer. PLAC8 also participates in the regulation of the cell cycle, autophagy, epithelial-mesenchymal transition and other cellular functions, indicating its potential as a molecular target worth further investigation. The present study investigated the effect of PLAC8 on the proliferation of lung adenocarcinoma PC-9 cells and their sensitivity to gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It was found that the inhibition of PLAC8 expression in PC-9 cells resulted in significantly decreased proliferation, whereas overexpression of PLAC8 significantly increased the proliferation (P<0.05) of PC-9 cells. Furthermore, inhibition of PLAC8 expression resulted in decreased activity of the ERK signaling pathway, while PLAC8 overexpression increased activity of this pathway. Inhibition of the ERK signaling pathway with U0126 reversed the effects induced by inhibiting or overexpressing PLAC8 on cell proliferation. In addition, overexpression of PLAC8 significantly decreased the sensitivity of PC-9 cells to gefitinib, and this effect was reversed by U0126. Overall, these results suggest that PLAC8 is involved in the regulation of proliferation of lung adenocarcinoma PC-9 cells and impacts their sensitivity to an EGFR-TKI. Thus, PLAC8 is a potential novel target in lung adenocarcinoma for future studies.

Multifaced roles of PLAC8 in cancer

“…PLAC8 overexpression decreases sensitivity to gemcitabine and oxaliplatin in gallbladder carcinoma cells [108]. Overexpression of PLAC8 significantly decreases the sensitivity of lung adenocarcinoma to gefitinib [45]. Taken together, these results suggest that PLAC8 may predict drug resistance in various cancer cells and be a promising therapeutic target.…”

“…We found that PLAC8 inhibits breast cancer cell apoptosis, thus promoting cell proliferation [34]. PLAC8 decreases the sensitivity of lung adenocarcinoma cells to gefitinib-induced apoptosis by reducing the expression of cleaved caspase 3 and cleaved PARP [45]. The mRNA levels of PLAC8 are increased in stool, and that its increased expression correlates with colorectal cells relapse [63,66].…”

“…As a key regulator of growth in different species, including fungi [43], plants [24,44] and mammals [3,30,45,46], PLAC8 participates in many important physiological activities in different contexts [31,[47][48][49]. Such as, the ratio of FAIM3:PLAC8 might be a diagnostic biomarker in sepsis [47].…”

Insight of Autophagy in Spontaneous Miscarriage

“…Effects followed with decreased PVT1 in villi samples might be involved in RSM pathogenesis, rendering PVT1 as a therapeutic target [199]. PLAC8, a newly-explored factor in tumorigenesis, has been regarded as a target of treating oral squamous cell carcinoma for its regulatory roles in ERK [201], Wnt/β-catenin and PI3K/Akt/GSK3β pathways [202], respectively. In trophoblasts, PLAC8 co-localizes with p53 and mediates its degradation, facilitating the viability, proliferation and differentiation via enhanced autophagy [106].…”

NEIL3 may act as a potential prognostic biomarker for lung adenocarcinoma

“…Lung adenocarcinoma (LUAD) is the most frequent pathological subtype, accounting for nearly 45% of lung cancer cases [ 2 ]. The 5-year relative survival rate of LUAD is only 5% because about 57% of patients are diagnosed with advanced stage and metastatic disease [ 3 , 4 ]. Patients with LUAD have improved overall survival (OS) after surgery and radiotherapy when diagnosed sooner.…”