Combined Evaluation of MAP1LC3B and SQSTM1 for Biological and Clinical Significance in Ductal Carcinoma of Breast Cancer.

Pei-Feng Liu,Hsiu-Chen Yang,Chih-Wen Shu,Luo-Ping Ger,Yen-Dun Tony Tzeng,Cheng-Hsin Lee,Wen-Ching Wang,Huei-Han Liou

doi:10.3390/biomedicines9111514

Pei-Feng Liu, Hsiu-Chen Yang + Show 6 more

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https://doi.org/10.3390/biomedicines9111514

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Breast cancer is the leading cause of cancer death in women worldwide. The microtubule-associated protein light chain 3B (MAP1LC3B) and adaptor sequestosome 1 (SQSTM1) are two major markers for autophagy. Increased protein levels of MAP1LC3B and SQSTM1 are considered to be causes of autophagy inhibition or activation in various types of cancers. However, the roles of MAP1LC3B and SQSTM1 in breast cancer are still not clear. Using a tissue microarray from 274 breast invasive ductal carcinoma (IDC) patients, we found that tumor tissues showed higher protein levels of MAP1LC3B and cytoplasmic SQSTM1 in comparison to those in adjacent normal tissues. Moreover, high levels of MAP1LC3B were associated with better survival, including disease-specific survival and disease-free survival (DFS) in IDC patients. Furthermore, high co-expression of MAP1LC3B and SQSTM1 was significantly associated with better DFS in IDC patients. Astonishingly, the autophagy inhibitor accumulated the protein levels of MAP1LC3B/SQSTM1 and enhanced the cytotoxic effects of cisplatin and paclitaxel in MCF7 and BT474 breast cancer cell lines, implying that autophagy inhibition might result in poor prognosis and chemosensitivity in IDC. Taken together, high co-expression of MAP1LC3B and SQSTM1 might serve as a potential diagnostic and prognostic biomarker for IDC patients.

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Accumulated protein levels of MAP1LC3B and SQSTM1 in treated breast cancer cell lines were observed (Figure 2A) and quantified (Figure 2B). These results indicate that the accumulation of MAP1LC3B and SQSTM1 might be caused by autophagy inhibition in breast cancer cell lines
The Live/Dead staining assay (Figure 4A) indicated that autophagy inhibitor CQ slightly reduced live MCF7 and BT474 cells (Figure 4B) but significantly increased dead MCF7 and BT474 cells (Figure 4C) in the presence of CIS and PTX. These results indicate that accumulated MAP1LC3B and SQSTM1 caused by autophagy inhibition might be involved in the chemoresistance of breast cancer cell lines
Our results find higher protein levels of MAP1LC3B and cytoplasmic SQSTM1 in the tumor tissues of invasive ductal carcinoma (IDC) patients

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Introduction

Breast cancer is the most prevalent type of malignancy among women and a major leading cause of cancer death worldwide. Breast invasive ductal carcinoma (IDC), a common type of breast cancer, comprises nearly 70–80% of all breast cancer [1]. Traditional classification systems in biological characteristics of molecular subtype specific proteins may have limitations for breast cancer patient-tailored treatment [2], suggesting the urgent need for effective diagnostic and prognostic biomarkers in breast cancer patients. Autophagy is crucial for physiological homeostasis, but its dysfunction causes many diseases including cancer, neurodegenerative diseases and infection.

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