The Role of Sox7 on the WNT Signaling Pathway in Lung Adenocarcinoma Público

Shen, Yishen (Spring 2023)

Permanent URL: https://etd.library.emory.edu/concern/etds/bn9997829?locale=pt-BR
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Abstract

Lung cancer is the most common form and a major cause of cancer death worldwide. Lung adenocarcinoma (LUAD) is the primary subtype of non-small cell lung cancer (NSCLC) which accounts for 80% to 85% of lung cancers. Sox7 is a transcriptional regulator, and it is a tumor suppressor in prostate, colon, and breast cancers. It is consistently downregulated or silenced in advanced tumors, including NSCLC. The canonical WNT signaling pathway is implicated in metastasis and relapse during LUAD progression. Sox7 suppresses β-catenin– mediated transcription by depleting active β-catenin (ABC) in the canonical WNT signaling pathway in prostate and colorectal cancer. After analyzing human specimens and cell line data, Sox7 was found to have a low mutation frequency, and its expression positively correlated with survival rate. Eight LUAD cell lines were identified and confirmed with low or high Sox7 expression. In both H358 and H522 LUAD cells, Sox7 ectopic expression led to lower proliferation, colony formation, and migration. In H358-Sox7, a G1 to S phase shift and decrease in ABC were observed. However, in H522-Sox7, no significant changes in cell cycle progression or β-catenin and ABC productions were observed. Upon introduction of β-catenin into H522 cells, WNT activity was elevated. Understanding the mechanisms behind H522 and H358 cells’ behavioral changes would require further exploration. To expand our findings into more cell lines, Sox7 knock down was performed in HOP-62, PC-9, and H1792, and increased migration abilities were exhibited in all three cell lines. Results from this study indicated that Sox7 inhibits LUAD’s proliferation and migration, but only alters WNT signaling in some LUAD cells.

Table of Contents

Introduction............................................................................................. .................................................................. 1 Hypothesis................................................................................................................... ...............................................2

Research Aims............................................................................................................................. .............................. 3

Methods and Materials................................................................................... ....................................................... 3 Results...................................................................................................................... ..................................................... 9 Discussion..................................................................................................................... ............................................ 17

Table and Figures................................................................................. ................................................................. 22 References.............................................................................................................. .................................................. 36

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