[논문]암 치료 표적으로써 cathepsin S

우선민; 권택규

doi:10.5352/jls.2018.28.6.753

암 치료 표적으로써 cathepsin S
Cathepsin S as a Cancer Therapeutic Target 원문보기

생명과학회지 = Journal of life science, v.28 no.6 = no.218, 2018년, pp.753 - 763

우선민 (계명대학교 의과대학 면역학교실) , 권택규 (계명대학교 의과대학 면역학교실)

초록
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Cathepsin은 리소좀에 존재하는 효소로, 엔도좀-리소좀 경로를 통하여 손상된 단백질의 분해를 유도한다. 이러한 cathepsin은 활성화되는 촉매 잔기 위치(catalytic residue site)에 따라 cysteine, aspartate, serine cathepsin으로 나뉜다. 다양한 암세포에서 cysteine cathepsin은 유전자 증폭이나 전사, 번역, 전사 후 단계를 통해 높은 발현을 유지한다. 특히 cathepsin S의 경우, 다른 cysteine cathepsin과 달리 중성 pH 환경에서도 안정적으로 활성도를 유지하며 특정 조직에서 발현이 제한적이라는 특징을 가지고 있기 때문에 질병의 미세환경에서 중요한 역할을 한다. 면역세포에서의 cathepsin S는 불변 사슬(invariant chain)을 분해하여 항원 제시에 중요한 MHC class II의 활성화를 통해 면역 반응을 조절하며, 암세포에서의 cathepsin S는 전이와 혈관신생을 조절함으로써 암세포의 성장을 증가시키는 역할을 한다. Cathepsin S의 발현 조절에 문제가 생기면 암, 관절염, 심혈관 질환을 포함한 많은 병리학적 현상에 영향을 미친다. 특히 암세포에서 cathepsin S의 발현 억제와 결함은 혈관신생을 억제시킬 뿐만아니라, 암세포의 성장과 전이를 감소시키고 세포사멸을 유도한다. 따라서, cathepsin S는 암 치료에 있어 좋은 표적이 될 수 있다.

Abstract ▼ AI-Helper

Cysteine cathepsins are lysosomal enzymes that belong to the papain family and can induce the degradation of damaged proteins through the endo-lysosomal pathway. It is highly upregulated in many cancers by regulating gene amplification and transcriptional, translational, and post-transcriptional modifications. Cathepsin S is part of the cysteine cathepsin family. Many studies have demonstrated that cathepsin S not only plays a specific role in MHC class II antigen presentation but also plays a crucial role in cancers. Cathepsin S is more stable at a neutral pH compared to other cysteine cathepsins, which supports the importance of cathepsin S in disease microenvironments. Therefore, the dysregulation of cathepsin S has participated in a variety of pathological processes, including cancer, arthritis, and cardiovascular disease. Furthermore, a decrease or depletion in the expression of cathepsin S has been implicated in the processes of tumor growth, invasion, metastasis, and angiogenesis. Taken together, cathepsin S has been suggested as an attractive therapeutic target for cancer therapy. In this review, the known involvement of cathepsin S in diseases, particularly with respect to recent work indicating its role in cancer therapy, is examined. An overview of current literature on the inhibitors of cathepsin S as a therapeutic target for cancer is also provided.

주제어

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문제 정의

반면, cathepsin K, W 및 S는 제한적인 조직에 분포되어 있기 때문에 특이성을 가진다. 본 보고에서는 cysteine cathepsin S의 조절을 통한 항암효과와 다양한 질병에서의 역할에 대해 기술하고자 한다.

성능/효과

많은 연구를 통하여 암의 진행에서 cysteine cathepsin의 역할을 확인하였으며, 특히 cathepsin S의 경우 혈관신생에 매우 중요하다[86]. 유전적으로 cathepsin S가 결핍된 모델에서 혈관신생이 감소할 뿐만 아니라 종양의 전이와 크기가 억제되며, 결과적으로 암세포사멸을 유도를 통해 종양의 성장을 막는다. 따라서, 종양의 성장과 진행에 있어서 cathepsin S의 역할이 중요하다[31].

후속연구

Cathepsin S를 타겟으로 한 항암 효과로는 apoptosis의 유도와 autophagy 매개 세포사멸의 증가 및 혈관신생과 전이 억제가 나타난다. 또한, cathepin S를 타겟으로 하는 저분자 물질을 이용하여 기존 항암제에 대한 저항성을 극복하고 더 강한 항암작용을 기대 할 수 있다. 따라서 cathepsin S는 다양한 병리학적 질환에서 질병의 진단과 예후를 예측할 수 있는 강력한 바이오마커로, 암을 포함한 여러 질환을 치료하는 데 있어 뛰어난 치료 표적이 될 것으로 생각한다.

질의응답

핵심어	질문	논문에서 추출한 답변
	리소좀은 무엇인가?	리소좀(Lysosome)은 최적 pH가 산성인 세포 내 소기관으로 protease, glycosidase, lipase, nuclease와 같은 50개가 넘는 가수분해효소를 가지고 있다. 따라서 endocytosis이나 식균작용(phagocytosis)에 의해 유입된 모든 유형의 거대분자를 분해하고 재사용 여부를 결정하기 때문에, 리소좀은 세포의 항상성 조절에 있어 매우 중요하다[2, 70].
	Protease가 단백질을 분해하는 방법은?	Protease는 공유결합으로 연결된 아미노산의 펩티드 결합을 가수분해시킴으로써 단백질을 분해하는 기능을 가진 효소이다[72]. 이러한 protease는 단순히 단백질의 분해와 합성을 조절할 뿐만 아니라 뼈를 재구성하거나 항원 제시 및 여러가지 질병과 같은 다양한 범위의 생리학적 과정에 영향을 미친다[29, 99, 102].
	Protease는 인체 내에서 어떤 영향을 미치는가?	Protease는 공유결합으로 연결된 아미노산의 펩티드 결합을 가수분해시킴으로써 단백질을 분해하는 기능을 가진 효소이다[72]. 이러한 protease는 단순히 단백질의 분해와 합성을 조절할 뿐만 아니라 뼈를 재구성하거나 항원 제시 및 여러가지 질병과 같은 다양한 범위의 생리학적 과정에 영향을 미친다[29, 99, 102]. 현재 많은 protease가 암이나 자가면역, 심혈관계 질환 및 신경 퇴행성질환을 치료하는 타겟으로 여겨지고 있다[59, 94, 96].

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