Mast cells inhibit colorectal cancer development by inducing ER stress through secreting Cystatin C

被引：15

作者：

Song, Feifei ^{[1
]}

Zhang, Youhua ^{[1
]}

Chen, Qi ^{[2
]}

Bi, Dexi ^{[1
]}

Yang, Muqing ^{[3
]}

Lu, Ling ^{[1
]}

Li, Man ^{[1
]}

Zhu, Huiyuan ^{[1
]}

Liu, Ying ^{[4
]}

Wei, Qing ^{[1
]}

Qin, Huanlong ^{[5
]}

Li, Jiyu ^{[4
,6
]}

机构：

[1] Tongji Univ, Dept Pathol, Shanghai Peoples Hosp 10, Shanghai 200072, Peoples R China

[2] Fudan Univ, Zhongshan Hosp, Dept Gastroenterol & Hepatol, Shanghai 200031, Peoples R China

[3] Tongji Univ, Ctr Difficult & Complicated Abdominal Surg, Shanghai Peoples Hosp 10, Shanghai 200072, Peoples R China

[4] Tongji Univ, Dept Gen Surg, Shanghai Peoples Hosp 10, Shanghai 200072, Peoples R China

[5] Tongji Univ, Dept Gastrointestinal Surg, Shanghai Peoples Hosp 10, Shanghai 200072, Peoples R China

[6] Fudan Univ, Geriatr Canc Ctr, HuaDong Hosp, Shanghai 200040, Peoples R China

来源：

ONCOGENE | 2023年 / 42卷 / 03期

基金：

中国国家自然科学基金;

关键词：

ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; PROGNOSTIC-SIGNIFICANCE; TUMOR ANGIOGENESIS; BREAST-CANCER; DENSITY; SURVIVAL; PATHWAY; PROGRESSION; CONTRIBUTE;

D O I：

10.1038/s41388-022-02543-z

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mast cells (MCs) are abundantly distributed in the human intestinal mucosa and submucosa. However, their roles and mechanisms in the development of colorectal cancer (CRC) are still unclear. In the present research, we found that the infiltration density of MCs in CRC tissues was positively correlated with improved patients' prognoses. Moreover, MCs suppressed the growth and induced the apoptosis of CRC cells in vitro and in vivo but had no effect on normal colonic epithelial cells. The present study revealed that MCs specifically induced endoplasmic reticulum stress (ERS) and activated the unfolded protein response (UPR) in CRC cells but not in normal cells, which led to the suppression of CRC development in vivo. Furthermore, we found that the secreted Cystatin C protein was the key factor for the MC-induced ERS in CRC cells. This work is of significance for uncovering the antitumor function of MCs in CRC progression and identifying the potential of CRC to respond to MC-targeted immunotherapy.

引用

页码：209 / 223

页数：15

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