Inhibition of SOX9 may be an effective target for increasing radiosensitivity in gastrointestinal cancer

Wei, Ming-Feng; Kuo, Sung‐Hsin

doi:10.21037/atm.2017.03.60

Cited by 4 publications

(2 citation statements)

References 13 publications

(9 reference statements)

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“…The physiological functions of SOX9 include cartilage formation, sex differentiation decision, nerve glial and heart development . In addition, it was found that the abnormal expression was related to many human disease and especially in tumours formation and development . SOX9 is over‐expressed in various cancers, such as colorectal cancer, prostate cancer, pancreatic cancer, lung cancer, brain cancer, and melanoma …”

Section: Introductionmentioning

confidence: 99%

Expression and correlation of MALAT1 and SOX9 in non‐small cell lung cancer

Chen

Zhao

Chen

et al. 2018

Clinical Respiratory J

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Section: Introductionmentioning

confidence: 99%

Expression and correlation of MALAT1 and SOX9 in non‐small cell lung cancer

Chen

Zhao

Chen

et al. 2018

Clinical Respiratory J

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“…Therefore, SOX9 may be a potential target for treatment of pulmonary fibrosis. The role of SOX9 in cancer has prompted interest in developing SOX9 inhibitors, which could be leveraged for the treatment of PF [118][119][120].…”

Section: The Igf-ii-sox9 Pathway In Human Lung Fibroblastsmentioning

confidence: 99%

The Role of SOX9 in IGF-II-Mediated Pulmonary Fibrosis

Waldrep

Rodgers

Garrett

et al. 2023

IJMS

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Pulmonary fibrosis (PF) associated with systemic sclerosis (SSc) results in significant morbidity and mortality. We previously reported that insulin-like growth factor-II (IGF-II) is overexpressed in lung tissues and fibroblasts from SSc patients, and IGF-II fosters fibrosis by upregulating collagen type I, fibronectin, and TGFβ. We now show that IGF-II augments mRNA levels of profibrotic signaling molecules TGFβ2 (p ≤ 0.01) and TGFβ3 (p ≤ 0.05), collagen type III (p ≤ 0.01), and the collagen posttranslational modification enzymes P4HA2 (p ≤ 0.05), P3H2 (p ≤ 0.05), LOX (p = 0.065), LOXL2 (p ≤ 0.05), LOXL4 (p ≤ 0.05) in primary human lung fibroblasts. IGF-II increases protein levels of TGFβ2 (p ≤ 0.01), as well as COL3A1, P4HA2, P4Hβ, and LOXL4 (p ≤ 0.05). In contrast, IGF-II decreases mRNA levels of the collagen degradation enzymes cathepsin (CTS) K, CTSB, and CTSL and protein levels of CTSK (p ≤ 0.05). The SRY-box transcription factor 9 (SOX9) is overexpressed in SSc lung tissues at the mRNA (p ≤ 0.05) and protein (p ≤ 0.01) levels compared to healthy controls. IGF-II induces SOX9 in lung fibroblasts (p ≤ 0.05) via the IGF1R/IR hybrid receptor, and SOX9 regulates TGFβ2 (p ≤ 0.05), TGFβ3 (p ≤ 0.05), COL3A1 (p ≤ 0.01), and P4HA2 (p ≤ 0.001) downstream of IGF-II. Our results identify a novel IGF-II signaling axis and downstream targets that are regulated in a SOX9-dependent and -independent manner. Our findings provide novel insights on the role of IGF-II in promoting pulmonary fibrosis.

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