FOXP3-regulated lncRNA NONHSAT136151 promotes colorectal cancer progression by disrupting QKI interaction with target mRNAs.

The role of lncRNAs in the pathogenesis of cancer, including colorectal cancer (CRC), has repeatedly been demonstrated. However, very few lncRNAs have been well annotated functionally. Our study identified a novel lncRNA upregulated in CRC, NONHSAT136151, which was correlated with clinical progression. In functional assays, NONHSAT136151 significantly enhanced CRC cell proliferation, migration and invasion. Mechanistically, NONHSAT136151 interacted with RNA-binding protein (RBP) QKI (Quaking) to interfere with QKI binding to target mRNAs and regulate their expression. As well, FOXP3 may be causally related to the dysregulation of NONHSAT136151 in CRC cells through its transcriptional activity. In conclusion, our findings identified a novel lncRNA regulated by FOXP3 participates in CRC progression through interacting with QKI, indicating a novel lncRNA-RBP interaction mechanism is involved in CRC pathogenesis.

Migration of fish bones into abdominal para-aortic tissue from the duodenum after leading to duodenal perforation: a case report.

BACKGROUND: Migration of fish bones into abdominal para-aortic tissue after penetrating the junction of 3rd and 4th part of duodenum is incredibly rare. CASE PRESENTATION: A 68-year-old man was admitted to our hospital with persistent colic in the lower abdomen after eating fish two weeks ago. Abdominal computed tomography (CT) scan showed High density streaks along the anterior and lower edges of the 3rd part of duodenum with peripheral exudation and localized peritonitis. Esophagogastroduodenoscopy didn't find foreign bodies and perforations in the digestive tract. Laparoscopic surgery and intraoperative endoscopy were made to detect foreign bodies and perforation site was found. After transition to open surgery, the fish bone was found in abdominal para-aortic tissue and removed without complications. Postoperative recovery is smooth, and the patient resumed normal diet and was discharged. CONCLUSIONS: It is difficult to choose a treatment plan for foreign bodies at the 3rd part of the duodenum, because it is difficult to judge the damage caused by the foreign body to the intestine and the positional relationship with the surrounding important organs. Conservative treatment or surgical treatment both have huge risks. The handling of this situation will extremely test the psychology, physical strength and professional experience of the surgeon.

INPP4B exerts a dual function in the stemness of colorectal cancer stem-like cells through regulating Sox2 and Nanog expression.

Inositol polyphosphate 4-phosphatase type II (INPP4B), a lipid phosphatase, was identified as a negative regulator of phosphatidylinositol 3-kinase (PI3K)/Akt signaling in several cancers. The expression and biological function of INPP4B in human colorectal cancer (CRC) are controversial, while the role and molecular mechanism of INPP4B in colorectal cancer stem-like cells (CR-CSLCs) remains unclear. Here, we observed that INPP4B expression was markedly decreased in primary non-metastatic CR-CSLCs and increased in highly metastatic CR-CSLCs compared with corresponding control non-CSLCs. INPP4B overexpression inhibited self-renewal, and chemoresistance of primary non-metastatic CR-CSLCs, but exerted the opposite roles in highly metastatic CR-CSLCs in vitro. Similarly, INPP4B knockdown had dual functions in the self-renewal and chemoresistance of different CR-CSLCs. In addition, we demonstrated that INPP4B overexpression suppressed the tumorigenicity of primary non-metastatic CR-CSLCs while induced the tumorigenicity of highly metastatic CR-CSLCs in nude mice. Furthermore, INPP4B was found to modulate the stemness of CR-CSLCs by regulating Sox2 and Nanog expression, which was dependent on PI3K/PTEN/Akt signaling. In conclusion, our results highlight an important role of INPP4B in the stemness of CR-CSLCs for the first time and emphasize INPP4B as a dual therapeutic target for suppressing primary cancer cell proliferation and for preventing metastasis in CRC patients.

Misdiagnosis of multiple myeloma as postoperative bone metastasis of rectal cancer: A case report and literature review.

Multiple myeloma (MM) and bone metastases are both common malignant tumors of the skeleton that share similar clinical manifestations and radiological features. The development of MM following rectal cancer surgery is relatively rare in clinical practice and is easily misdiagnosed as bone metastasis. The present study reported on a patient with MM and postoperative rectal cancer. A 65-year-old man had been diagnosed with low rectal cancer (poorly differentiated, T3N1M0) 10 years prior and underwent curative treatment at that time. During the 6-year follow-up period, no recurrence or metastasis of rectal cancer was detected. The patient was evaluated for bone pain 4 years ago and underwent multiple imaging examinations, including computed tomography (CT), magnetic resonance imaging, emission CT and positron emission tomography/CT at several well-known hospitals in China. All of these hospitals diagnosed the patient with bone metastasis from rectal cancer, in view of the earlier history. The patient's condition did not show any significant improvement despite treatment for bone metastasis. Subsequently, 3 years ago, the patient underwent surgical treatment at our hospital (Affiliated Hospital of Zunyi Medical University, Zunyi, China) for a hernia near the colostomy site combined with incomplete intestinal obstruction. Post-operatively, the patient developed a hematoma in the surgical area, along with stubborn anemia and abnormal coagulation function. No improvement was observed with hemostasis and multiple blood transfusions. The bone marrow smear was consistent with MM, with a significant elevation in serum IgA and ß2 microglobulin. The patient was ultimately diagnosed with MM (IgA-λ type), stage III, according to the Durie-Salmon staging system. The patient's condition improved with treatment for MM.

Advances in the role of long non­coding RNAs and RNA­binding proteins in regulating DNA damage repair in cancer cells.

DNA damage and repair play a crucial role in the development, progression and treatment of cancer. In response to various types of DNA damage, the organism initiates a series of DNA damage responses that trigger post­DNA damage repair processes. Among the most severe forms of DNA damage are DNA double­strand breaks (DSBs), which can be repaired by the body through two pathways: Homologous recombination and non­homologous end joining. The repair of DNA damage, particularly DNA DSBs, significantly influences the sensitivity and resistance of cancer cells to chemotherapy and radiotherapy. Numerous studies have demonstrated that long non­coding RNAs (lncRNAs) can exert multiple regulatory effects on cancer cells by binding to RNA binding proteins (RBPs), thereby influencing DNA damage repair. Based on a comprehensive literature search, the existing research on the regulation of DNA damage repair by lncRNAs interacting with RBPs has primarily focused on the repair of DNA DSBs. Therefore, the present review discusses the regulatory effects of the interaction between lncRNAs and RBPs on DNA damage repair in cancer cells, with a specific focus on the repair of DNA DSBs and its implications in cancer. It is hoped that comprehensive analysis may enhance the current understanding of the molecular mechanisms underlying DNA damage repair in cancer and may lead to the identification of novel diagnostic biomarkers and potential therapeutic targets.

The crosstalk of CD8+ T cells and ferroptosis in cancer.

Ferroptosis is an iron-dependent, novel form of programmed cell death characterized by lipid peroxidation and glutathione depletion and is widespread in a variety of diseases. CD8+ T cells are the most important effector cells of cytotoxic T cells, capable of specifically recognizing and killing cancer cells. Traditionally, CD8+ T cells are thought to induce cancer cell death mainly through perforin and granzyme, and Fas-L/Fas binding. In recent years, CD8+ T cell-derived IFN-γ was found to promote cancer cell ferroptosis by multiple mechanisms, including upregulation of IRF1 and IRF8, and downregulation of the system XC-, while cancer cells ferroptosis was shown to enhance the anti-tumor effects of CD8+ T cell by heating the tumor immune microenvironment through the exposure and release of tumor-associated specific antigens, which results in a positive feedback pathway. Unfortunately, the intra-tumoral CD8+ T cells are more sensitive to ferroptosis than cancer cells, which limits the application of ferroptosis inducers in cancer. In addition, CD8+ T cells are susceptible to being regulated by other immune cell ferroptosis in the TME, such as tumor-associated macrophages, dendritic cells, Treg, and bone marrow-derived immunosuppressive cells. Together, these factors build a complex network of CD8+ T cells and ferroptosis in cancer. Therefore, we aim to integrate relevant studies to reveal the potential mechanisms of crosstalk between CD8+ T cells and ferroptosis, and to summarize preclinical models in cancer therapy to find new therapeutic strategies in this review.

Effects of Different Levels of Surgical Separation on Neck Bulge and Swallowing Disorders during Endoscopic Thyroidectomy.

OBJECTIVE: Our study aims to compare the effects of different levels of access on postoperative neck bulge and swallowing disorder and provide a better level for endoscopic thyroidectomy. MATERIALS AND METHODS: The patients were selected retrospectively between March 2021 to September 2021 by the Department of Thyroid Surgery, Third Affiliated Hospital of Zunyi Medical University. They were divided into two groups according to the level of the free flap during surgery: group A (the superficial cervical fascial level) and group B (the superficial deep cervical fascial level). Age, sex, body mass index, diameter of the primary lesion, postoperative neck bulge, and swallowing disorders and other complications were compared between the two groups. RESULTS: A total of 40 patients who underwent endoscopic unilateral lobectomy plus central region lymph node dissection were enrolled in our study. Twenty in group A and 20 in group B. The age, gender, body mass index, diameter, and the proportion of benign and malignant primary lesions were not significantly different between the two groups ( P >0.05), and there was also no difference in thyroid function between the two groups ( P >0.05). No significant differences were observed in terms of bleeding and operation time during the operation ( P >0.05). There were also no statistical differences in terms of recurrent laryngeal nerve injury or hypoparathyroidism ( P >0.05). However, patients in group B were superior to those in group A in the occurrence of neck bulge and swallowing disorders ( P <0.05). These symptoms were most evident one month after surgery. Six months after the operation, only 4 patients in group B still complained of neck "swelling" and uncomfortable straining which did not resolve until 1 year after the operation. No statistical significance between long-term results and complication rates could be observed in either group. CONCLUSION: In endoscopic thyroidectomy, the superficial cervical fascial level may be a better option for reducing postoperative neck bulge and swallowing disorders, which needs further validation by conducting a large sample study.

Research progress on the interaction between long non­coding RNAs and RNA­binding proteins to influence the reprogramming of tumor glucose metabolism (Review).

As epigenetic regulators, long non­coding RNAs (lncRNAs) are involved in various important regulatory processes and typically interact with RNA­binding proteins (RBPs) to exert their core functional effects. An increasing number of studies have demonstrated that lncRNAs can regulate the occurrence and development of cancer through a variety of complex mechanisms and can also participate in tumor glucose metabolism by directly or indirectly regulating the Warburg effect. As one of the metabolic characteristics of tumor cells, the Warburg effect provides a large amount of energy and numerous intermediate products to meet the consumption demands of tumor metabolism, providing advantages for the occurrence and development of tumors. The present review article summarizes the regulatory effects of lncRNAs on the reprogramming of glucose metabolism after interacting with RBPs in tumors. The findings discussed herein may aid in the better understanding of the pathogenesis of malignancies, and may provide novel therapeutic targets, as well as new diagnostic and prognostic markers for human cancers.

Clinical characteristics and prognosis of gastrointestinal stromal tumors with rare site metastasis (Review).

Gastrointestinal stromal tumors (GIST) are the most common stromal-derived tumors of the gastrointestinal tract and have a potential metastatic capacity in almost half of all cases, with the most common sites of metastasis being the liver and peritoneum. However, there is evidence that GIST metastasizes to sites other than the liver and peritoneum, which poses challenges for clinical diagnosis and treatment. Therefore, the Cochrane and Medline databases were searched via PubMed in July 2022 using relevant keywords to acquire the literature associated with the metastasis of GIST to rare sites published since from 2000 onwards. Study data comprising age, sex, primary location, metastatic site, mean survival time, clinical signs and symptoms, imaging, pathological features immunohistochemical indices, treatment and prognosis were recorded and analyzed. The 118 metastases at rare sites reported in the literature included bone (n=31), lung (n=10), lymph nodes (n=13), intracranial sites (n=13), skin and subcutaneous tissue (n=10), heart (n=7), skeletal muscle (n=7), orbit and choroid (n=6), pancreas (n=3), spleen (n=2), bone marrow (n=1), testis (n=3), scrotum (n=1), epididymis (n=1), penis (n=1), ovary (n=2), cervix (n=1), kidney (n=1), bladder (n=1), adrenal gland (n=2) and thyroid gland (n=2). From the reviewed studies, it may be concluded that when metastases from gastrointestinal stromal tumors occur at rare sites, the initial symptoms may help in the identification of these sites. In addition, the site-dependent imaging of different metastatic locations may further define the metastases, and the findings of pathological or immunohistochemical analyses may be used to confirm the diagnosis.

Research progress in the establishment of pancreatic cancer models and preclinical applications.

Pancreatic cancer (PC) is a highly malignant tumor in the digestive system. The transformation of tissue from normal to pancreatic intraepithelial neoplasm is driven by certain oncogenes, among which the mutation rate of the KRAS gene is as high as 90%. Currently, PC has limited treatment options, low therapeutic effects, and poor prognosis. Thus, more effective methods to combat PC are urgently needed. Some models that can more accurately reflect the biological behaviors and genomic characteristics of PC, such as its morphology, pathology, proliferation, and invasion, are being continuously developed. These include genetic engineering models, orthotopic xenograft models, and heterotopic xenograft models. Using these PC models, scientists have further verified promising drugs and potential therapeutic targets for PC treatment. This is of great significance for limiting the progression of PC with clinical intervention, improving patient outcomes, and improving survival rates.

Long non­coding RNAs interact with RNA­binding proteins to regulate genomic instability in cancer cells (Review).

Genomic instability, a feature of most cancers, contributes to malignant cell transformation and cancer progression due to the accumulation of genetic alterations. Genomic instability is reflected at numerous levels, from single nucleotide to the chromosome levels. However, the exact molecular mechanisms and regulators of genomic instability in cancer remain unclear. Growing evidence indicates that the binding of long non­coding RNAs (lncRNAs) to protein chaperones confers a variety of regulatory functions, including managing of genomic instability. The aim of the present review was to examine the roles of mitosis, telomeres, DNA repair, and epigenetics in genomic instability, and the mechanisms by which lncRNAs regulate them by binding proteins in cancer cells. This review contributes to our understanding of the role of lncRNAs and genomic instability in cancer and can potentially provide entry points and molecular targets for cancer therapies.

Interactions between long non­coding RNAs and RNA­binding proteins in cancer (Review).

Long non­coding RNAs (lncRNAs) fulfill important roles in the majority of cellular processes. Previous studies have demonstrated that lncRNAs are involved in the pathogenesis of various diseases, including cancer. However, to date, the functions of only a small number of the known lncRNAs have been well­documented. lncRNAs comprise a class of multifunctional non­coding transcripts that are able to interact with different types of biomolecules. Interactions between lncRNAs and RNA­binding proteins (RBPs) provide an important mechanism through which lncRNAs exert their regulatory functions, mainly through findings on 'generalized RBPs'. Regulatory effects on lncRNAs mediated by RBPs have also been explored. Taking account of the research that has been completed to date, the continued and in­depth study of the bidirectional interactions between lncRNAs and RBPs will prove to be of major importance for understanding the pathogenesis of cancer and for developing effective therapies. The present review aims to explore the interactions between lncRNAs and RBPs that have been investigated in cancer, taking into consideration several different aspects, including the regulation of expression, subcellular localization and the mediation of diverse functions.

Delayed diagnosis of ascending colon mucinous adenocarcinoma with local abscess as primary manifestation: Report of three cases.

BACKGROUND: Colorectal mucinous adenocarcinoma is a distinct subtype of colorectal adenocarcinoma that is not sensitive to chemotherapy and radiotherapy, and its prognosis is worse than that of nonmucinous adenocarcinoma. Early diagnosis and aggressive surgical treatment may be the key to improving the prognosis of patients. Ascending colon mucinous adenocarcinoma with the primary manifestation of a local abscess caused by non-intestinal perforation has never been reported. Moreover, since the lumen of the ascending colon is large, and early stage ascending colon cancer lacks typical clinical manifestations, the diagnosis may be delayed easily. We herein report three cases of delayed diagnosis of colorectal mucinous adenocarcinoma. CASE SUMMARY: We present three patients (two females and one male) with mucinous ascending colon mucinous adenocarcinoma with the primary manifestation of a local abscess (the right area of the lumbar spine, right groin, and lower right abdomen) caused by non-intestinal perforation. At the initial clinical visit, the common causes of those abscesses, including spinal tuberculosis and urinary tract infection, were excluded. The treatment of the abscess was through an incision and drainage. However, the source of the abscess was not made clear, which led to an abscess recurrence and a delayed diagnosis of colorectal mucinous adenocarcinoma. After the patients were referred to our hospital, a definitive diagnosis of ascending colon mucinous adenocarcinoma was made with the help of tumor markers and colonoscopic findings. Because of the delayed diagnosis of the disease, two patients (case 1 and case 2) missed the chance of surgery due to disease progression and died in a short follow-up period. Only case 3 underwent radical surgery for the tumor in the right colon and partial abdominal wall resection and achieved a better prognosis. CONCLUSION: Abscesses in the right area of the lumbar spine, right groin, or right lower quadrant caused by non-intestinal perforation as the primary clinical manifestation of ascending colon mucinous adenocarcinoma are extremely rare. Mucinous adenocarcinoma of the ascending colon may be one of the causes of such abscesses. Performing colonoscopy as soon as possible is of great significance in the diagnosis and treatment of the disease.

Comparison of Long-Term and Perioperative Outcomes of Robotic Versus Conventional Laparoscopic Gastrectomy for Gastric Cancer: A Systematic Review and Meta-Analysis of PSM and RCT Studies.

BACKGROUND: To investigate the perioperative and oncological outcomes of gastric cancer (GC) after robotic versus laparoscopic gastrectomy (RG versus LG), we carried out a meta-analysis of propensity score matching (PSM) studies and randomized controlled study (RCT) to compare the safety and overall effect of RG to LG for patients with GC. METHODS: PubMed, Web of Science, EMBASE, and Cochrane Central Register were searched based on a defined search strategy to identify eligible PSM and RCT studies before July 2021. Data on perioperative and oncological outcomes were subjected to meta-analysis. RESULTS: Overall, we identified 19 PSM studies and 1 RCT of RG versus LG, enrolling a total of 13,446 patients (6,173 and 7,273 patients underwent RG and LG, respectively). The present meta-analysis revealed nonsignificant differences in tumor size, proximal resection margin distance, distal resection margin distance, abdominal bleeding, ileus, anastomosis site leakage, duodenal stump leakage rate, conversion rate, reoperation, overall survival rate, and long-term recurrence-free survival rate between the two groups. Alternatively, comparing RG with LG, RG has a longer operative time (p < 0.00001), less blood loss (p <0.0001), earlier time to first flatus (p = 0.0003), earlier time to oral intake (p = 0.0001), shorter length of stay (p = 0.0001), less major complications (p = 0.0001), lower overall complications (p = 0.0003), more retrieved lymph nodes (P < 0.0001), and more cost (p < 0.00001). CONCLUSIONS: In terms of oncological adequacy and safety, RG is a feasible and effective treatment strategy for gastric cancer but takes more cost in comparison with LG.

MicroRNA­8063 targets heterogeneous nuclear ribonucleoprotein AB to inhibit the self­renewal of colorectal cancer stem cells via the Wnt/ß­catenin pathway.

The presence of cancer stem cells (CSCs) is a major cause of therapeutic failure in a variety of cancer types, including colorectal cancer (CRC). However, the underlying mechanisms that regulate the self­renewal of colorectal cancer stem cells (CRCSCs) remain unclear. Our previous study utilized CRCSCs and their parent cells; through gene microarray screening and bioinformatics analysis, we hypothesized that microRNA (miR)­8063 may bind to, and regulate the expression of, heterogeneous nuclear ribonucleoprotein AB (hnRNPAB) to facilitate the regulation of CRCSC self­renewal. The aim of the present study was to confirm this conjecture through relevant experiments. The results indicated that compared with that in parent cells, miR­8063 expression was significantly downregulated in CRCSCs, while hnRNPAB expression was increased. Furthermore, hnRNPAB was identified as a direct target of miR­8063 using a dual­Luciferase assay. Overexpression of hnRNPAB promoted the acquisition of CSC characteristics in CRC cells (increased colony formation ability, enhanced tumorigenicity, and upregulated expression of CSC markers), as well as the upregulation of key proteins (Wnt3a, Wnt5a and ß­catenin) in the Wnt/ß­catenin signaling pathway. Similarly, after silencing miR­8063 in CRC cells, the characteristics of CSC were altered, and the expression of hnRNPAB protein was promoted. However, post overexpression of miR­8063 in CRCSCs, the self­renewal ability of CSCs was weakened with the downregulation of hnRNPAB protein, Wnt3a, Wnt5a and ß­catenin. These results suggest that as a tumor suppressor, miR­8063 is involved in regulating the self­renewal of CRCSCs, where loss of miR­8063 expression weakens its inhibition on hnRNPAB, which leads to the activation of Wnt/ß­catenin signaling to promote the self­renewal of CRCSCs.

OCT4B1 Promoted EMT and Regulated the Self-Renewal of CSCs in CRC: Effects Associated with the Balance of miR-8064/PLK1.

Cancer stem cells (CSCs) are the main cause of tumor generation, recurrence, metastasis, and therapy failure in various malignancies including colorectal cancer (CRC). Accumulating evidence suggests that tumor cells can acquire CSC characteristics through the epithelial-mesenchymal transition (EMT) process. However, the molecular mechanism of CSCs remains unclear. OCT4B1 is a transcript of OCT4, which is initially expressed in embryonic stem and carcinoma cells, and is involved in the regulation and maintenance of an undifferentiated state of stem cells. In this study, three-dimensional (3D) microspheres were confirmed as CRC stem cells. Compared with that of parental cells, their self-renewal ability was significantly increased, and OCT4B1 expression was increased and promoted the EMT process. The knockdown of OCT4B1 decreased the self-renewal of CSCs and reversed EMT. Moreover, OCT4B1 induced the expression of Polo-like kinase 1 (PLK1), which is a key regulator of EMT in tumor cells. Further examination showed that OCT4B1 regulated the miR-8064/PLK1 balance to exert its function. Taken together, our data suggest that OCT4B1 may be involved in regulating the self-renewal of colorectal CSCs through EMT, which is at least partially due to the miR-8064/PLK1 balance. This study indicates that OCT4B1 is a potential therapeutic target for CRC by targeting CSCs.

High hnRNP AB expression is associated with poor prognosis in patients with colorectal cancer.

Heterogeneous ribonucleoprotein AB (hnRNP AB) is a member of the heterogeneous nuclear ribonucleoprotein family, which serves important functions in gene expression and signal transduction. However, the expression and clinicopathological significance of hnRNP AB in colorectal cancer (CRC) remain to be elucidated. To investigate the expression and clinical significance of hnRNP AB in CRC, hnRNP AB expression levels were analysed in two independent cohorts of patients with CRC. The results of reverse transcription-quantitative PCR, immunohistochemistry and western blot analysis demonstrated that hnRNP AB was upregulated in CRC tissues compared with the corresponding adjacent normal tissues. Immunohistochemical analyses indicated that a high expression of hnRNP AB was significantly associated with preoperative carcinoembryonic antigen (CEA; P<0.001) and carbohydrate antigen 19-9 (P=0.014) levels, tumour size (P=0.022) and infiltration (P=0.026), lymph node metastasis (P<0.001) and Tumour-Node-Metastasis stage (P<0.001). Univariate and multivariate Cox survival analyses revealed that hnRNP AB expression and preoperative CEA levels were significant independent factors affecting overall survival in patients with CRC (P<0.05). According to the Kaplan-Meier model, patients with CRC with high hnRNP AB expression exhibited significantly poorer prognosis compared with those with low hnRNP AB expression (P<0.001). In conclusion, the results of the present study demonstrated that hnRNP AB expression may serve an important role in the progression of CRC and that hnRNP AB may be considered a predictor of prognosis for patients with CRC.

The PEAK1-PPP1R12B axis inhibits tumor growth and metastasis by regulating Grb2/PI3K/Akt signalling in colorectal cancer.

Pseudopodium enriched atypical kinase 1 (PEAK1), a novel non-receptor tyrosine kinase, was recently implicated in cancer pathogenesis. However, its functional role in colorectal cancer (CRC) is not well known. Herein, we demonstrated that PEAK1 was frequently downregulated in CRC and significantly associated with tumor size, differentiation status, metastasis, and clinical stage. PEAK1 overexpression suppressed CRC cell growth, invasion, and metastasis in vitro and in vivo, whereas knockout had the opposite effects. Further evaluation revealed that PEAK1 expression was positively correlated with protein phosphatase 1 regulatory subunit 12B (PPP1R12B) in CRC cell lines and clinical tissues, and this protein was found to suppress activation of the Grb2/PI3K/Akt pathway. Moreover, PPP1R12B knockdown markedly abrogated PEAK1-mediated tumor suppressive effects, whereas its upregulation recapitulated the effects of PEAK1 knockout on cell behaviours and the activation of signalling. Mechanistically, PI3K and Akt inhibitors reversed impaired the effect of PEAK1 function on cell proliferation, migration, and invasion. Our results provide compelling evidence that the PEAK1-PPP1R12B axis inhibits colorectal tumorigenesis and metastasis through deactivation of the Grb2/PI3K/Akt pathway, which might provide a novel therapeutic strategy for CRC treatment.