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PINK1 promotes the progression of lung squamous cell carcinoma through the FAK/AKT/RhoA/vinculin pathway

  • Authors:
    • Xu Li
    • Yuhui Ma
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, Shanxi 030032, P.R. China, Department of Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, Shanxi 030032, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 195
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    Published online on: September 29, 2026
       https://doi.org/10.3892/or.2026.9201
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Abstract

Lung squamous cell carcinoma (LUSC) is an aggressive malignancy with a poor prognosis. Given the association between mitochondrial dysregulation and LUSC, the aim of the present study was to identify mitochondrial unfolded protein response (UPRmt)‑related candidate genes associated with LUSC and to explore their potential functional relevance. In the present study, differential expression, univariate Cox and survival analyses were combined to identify a UPRmt‑associated key gene in LUSC. Gene set enrichment analysis was then performed, and overexpression (OE) and knockdown cell lines were used to clarify its function using western blotting, Cell Counting Kit‑8, colony formation and Transwell® invasion assays. Using bioinformatics tools and a review of the literature, PTEN‑induced kinase 1 (PINK1) was singled out as a key gene in LUSC samples. Elevated PINK1 expression was associated with worse survival outcomes. A total of 117 pathways were enriched by PINK1, with the top 5 including ‘focal adhesion’ and ‘mitogen‑activated protein kinase signaling pathway’. Using experimental analysis, it was observed that PINK1 significantly enhanced the proliferative, migratory, invasive and colony forming abilities of tumor cells, thereby exacerbating LUSC. Furthermore, these enhancements were diminished by the application of focal adhesion kinase (FAK) inhibitor. It was also noted that the expression levels of protein kinase B (AKT), p‑AKT, Ras homolog family member A (RhoA) and vinculin were all elevated in OE‑PINK1 cells. Collectively, these findings indicated that PINK1 exerted its influence on LUSC through the FAK/AKT/RhoA/vinculin pathway. The present study identified PINK1 as a key gene in LUSC, exerting its influence through the FAK/AKT/RhoA/vinculin pathway, thereby presenting a potential novel therapeutic target for the treatment of LUSC in the future.
View Figures

Figure 1

PINK1 was selected as a key gene in
LUSC. (A) Differential expression levels of mitochondrial unfolded
protein response-related genes between LUSC and control samples.
(B) Analysis of LUSC survival-associated genes. Survival difference
of genes in (C) training and (D) validation sets. **P<0.01,
***P<0.001 and ****P<0.0001. ns, no significance; PINK1,
PTEN-induced kinase 1; LUSC, lung squamous cell carcinoma; TCGA,
The Cancer Genome Atlas; GEO, Gene Expression Omnibus; CEBPB,
CCAAT/enhancer-binding protein β; CLPP, caseinolytic mitochondrial
matrix peptidase proteolytic subunit; HTRA2, high-temperature
requirement A2.

Figure 2

Potential functions of PINK1
expression in LUSC. (A) DEGs between PINK1 high- and low-expression
groups. (B) Gene Ontology and (C) KEGG enrichment analysis of DEGs.
(D) Gene set enrichment analysis of DEGs. (E) GSVA between high-
and low-expression groups. PINK1, PTEN-induced kinase 1; LUSC, lung
squamous cell carcinoma; DEGs, differentially expressed genes;
KEGG, Kyoto Encyclopedia of Genes and Genomes; GSVA, gene set
variation analysis; ARVC, arrhythmogenic right ventricular
cardiomyopathy; ECM, extracellular matrix.

Figure 3

Immune and mutation landscape between
high- and low-expression groups. (A) Immune landscape in distinct
expression groups. (B) Difference in immune cell infiltration
between high- and low-expression groups. (C) Difference and (D)
correlation of the TIDE score between high- and low-expression
groups. (E) Difference in immune, stromal and ESTIMATE scores
between high- and low-expression groups. (F) Expression levels of
PINK1 among different immune cell subtypes. Statistical
significance was assessed using the Kruskal-Wallis test followed by
Dunn's post hoc multiple comparisons test with Holm correction for
multiple comparisons. (G) Mutation landscape of genes (left,
high-expression group; right, low-expression group). ns, no
significance; TIDE, tumor immune dysfunction and exclusion; PINK1,
PTEN-induced kinase 1; TMB, tumor mutation burden; TIDE, Tumor
Immune Dysfunction and Exclusion; NK, natural killer; ESTIMATE,
Estimation of STromal and Immune cells in MAlignant Tumor tissues
using Expression data.

Figure 4

PINK1 expression is associated with
mutation landscape and chemotherapy resistance in lung squamous
cell carcinoma. Expression levels of OE-PINK1 at the (A) mRNA and
(B) protein levels. Expression levels of sh-PINK1 at the (C) mRNA
and (D) protein levels. (E) Cell activity of OE- and sh-PINK1. (F)
Colony formation of OE- and sh-PINK1. (G) Migration and invasion of
OE- and sh-PINK1. PINK1, PTEN-induced kinase 1; shRNA/sh, short
hairpin RNA; OE, overexpression; NC, negative control; KD,
knockdown.

Figure 5

PINK1 promotes lung squamous cell
carcinoma through the FAK/AKT/RhoA/vinculin pathway. (A) Protein
expression levels of FAK and p-FAK, as well as the p-FAK/FAK ratio.
(B) Cell activity with FAK inhibitor. (C) Migration and invasion
with FAK inhibitor. (D) Colony formation with FAK inhibitor.
Protein expression levels of (E) AKT and p-AKT (and the p-AKT/AKT
ratio), (F) RhoA and (G) vinculin. PINK1, PTEN-induced kinase 1;
FAK/AKT/RhoA, focal adhesion kinase/protein kinase B/Ras homolog
family member A; p, phosphorylated; OE, overexpression; NC,
negative control.
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Copy and paste a formatted citation
Spandidos Publications style
Li X and Ma Y: PINK1 promotes the progression of lung squamous cell carcinoma through the FAK/AKT/RhoA/vinculin pathway. Oncol Rep 56: 195, 2026.
APA
Li, X., & Ma, Y. (2026). PINK1 promotes the progression of lung squamous cell carcinoma through the FAK/AKT/RhoA/vinculin pathway. Oncology Reports, 56, 195. https://doi.org/10.3892/or.2026.9201
MLA
Li, X., Ma, Y."PINK1 promotes the progression of lung squamous cell carcinoma through the FAK/AKT/RhoA/vinculin pathway". Oncology Reports 56.5 (2026): 195.
Chicago
Li, X., Ma, Y."PINK1 promotes the progression of lung squamous cell carcinoma through the FAK/AKT/RhoA/vinculin pathway". Oncology Reports 56, no. 5 (2026): 195. https://doi.org/10.3892/or.2026.9201
Copy and paste a formatted citation
x
Spandidos Publications style
Li X and Ma Y: PINK1 promotes the progression of lung squamous cell carcinoma through the FAK/AKT/RhoA/vinculin pathway. Oncol Rep 56: 195, 2026.
APA
Li, X., & Ma, Y. (2026). PINK1 promotes the progression of lung squamous cell carcinoma through the FAK/AKT/RhoA/vinculin pathway. Oncology Reports, 56, 195. https://doi.org/10.3892/or.2026.9201
MLA
Li, X., Ma, Y."PINK1 promotes the progression of lung squamous cell carcinoma through the FAK/AKT/RhoA/vinculin pathway". Oncology Reports 56.5 (2026): 195.
Chicago
Li, X., Ma, Y."PINK1 promotes the progression of lung squamous cell carcinoma through the FAK/AKT/RhoA/vinculin pathway". Oncology Reports 56, no. 5 (2026): 195. https://doi.org/10.3892/or.2026.9201
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